array:24 [
  "pii" => "S2173511506704201"
  "issn" => "21735115"
  "doi" => "10.1016/S2173-5115(06)70420-1"
  "estado" => "S300"
  "fechaPublicacion" => "2006-09-01"
  "aid" => "70420"
  "copyright" => "Sociedade Portuguesa de Pneumologia"
  "copyrightAnyo" => "2006"
  "documento" => "article"
  "crossmark" => 0
  "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/"
  "subdocumento" => "rev"
  "cita" => "Rev Port Pneumol. 2006;12:545-61"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 2755
    "formatos" => array:3 [
      "EPUB" => 232
      "HTML" => 1651
      "PDF" => 872
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2173511506704213"
    "issn" => "21735115"
    "doi" => "10.1016/S2173-5115(06)70421-3"
    "estado" => "S300"
    "fechaPublicacion" => "2006-09-01"
    "aid" => "70421"
    "copyright" => "Sociedade Portuguesa de Pneumologia"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/"
    "subdocumento" => "rev"
    "cita" => "Rev Port Pneumol. 2006;12:563-79"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 3479
      "formatos" => array:3 [
        "EPUB" => 235
        "HTML" => 1768
        "PDF" => 1476
      ]
    ]
    "pt" => array:10 [
      "idiomaDefecto" => true
      "titulo" => "Doenças inflamatórias alérgicas das vias aéreas superiores e suas implicações na asma brônquica – A propósito de um caso clínico"
      "tienePdf" => "pt"
      "tieneTextoCompleto" => 0
      "tieneResumen" => array:2 [
        0 => "pt"
        1 => "en"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "563"
          "paginaFinal" => "579"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "Allergic inflammatory diseases of the upper airways and their impact on asthma – Following on from a case report"
        ]
      ]
      "contieneResumen" => array:2 [
        "pt" => true
        "en" => true
      ]
      "contienePdf" => array:1 [
        "pt" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Ana L. Fonseca, Ana M. Arrobas"
          "autores" => array:2 [
            0 => array:2 [
              "nombre" => "Ana L."
              "apellidos" => "Fonseca"
            ]
            1 => array:2 [
              "nombre" => "Ana M."
              "apellidos" => "Arrobas"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "pt"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173511506704213?idApp=UINPBA00004E"
    "url" => "/21735115/0000001200000005/v1_201305151428/S2173511506704213/v1_201305151428/pt/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S2173511506704195"
    "issn" => "21735115"
    "doi" => "10.1016/S2173-5115(06)70419-5"
    "estado" => "S300"
    "fechaPublicacion" => "2006-09-01"
    "aid" => "70419"
    "copyright" => "Sociedade Portuguesa de Pneumologia"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/"
    "subdocumento" => "fla"
    "cita" => "Rev Port Pneumol. 2006;12:539-44"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 2446
      "formatos" => array:3 [
        "EPUB" => 234
        "HTML" => 1275
        "PDF" => 937
      ]
    ]
    "en" => array:10 [
      "idiomaDefecto" => true
      "titulo" => "Respiratory squamous cell carcinomas in vibroacoustic disease"
      "tienePdf" => "en"
      "tieneTextoCompleto" => 0
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "pt"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "539"
          "paginaFinal" => "544"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "pt" => array:1 [
          "titulo" => "Carcinomas epidermóides do pulmão na doença vibroacústica"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "pt" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "José Reis Ferreira, Carla P. Mendes, Mariana Alves-Pereira, Nuno A.A. Castelo Branco"
          "autores" => array:4 [
            0 => array:2 [
              "nombre" => "José"
              "apellidos" => "Reis Ferreira"
            ]
            1 => array:2 [
              "nombre" => "Carla P."
              "apellidos" => "Mendes"
            ]
            2 => array:2 [
              "nombre" => "Mariana"
              "apellidos" => "Alves-Pereira"
            ]
            3 => array:2 [
              "nombre" => "Nuno A.A."
              "apellidos" => "Castelo Branco"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173511506704195?idApp=UINPBA00004E"
    "url" => "/21735115/0000001200000005/v1_201305151428/S2173511506704195/v1_201305151428/en/main.assets"
  ]
  "pt" => array:15 [
    "idiomaDefecto" => true
    "titulo" => "Cancro do pulmão na mulher: Uma entidade diferente?"
    "tieneTextoCompleto" => 0
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "545"
        "paginaFinal" => "561"
      ]
    ]
    "autores" => array:1 [
      0 => array:3 [
        "autoresLista" => "Renato Sotto-Mayor"
        "autores" => array:1 [
          0 => array:4 [
            "nombre" => "Renato"
            "apellidos" => "Sotto-Mayor"
            "email" => array:1 [
              0 => "renato.sottomayor@hsm.min-saude.pt"
            ]
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">2</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:1 [
          0 => array:3 [
            "entidad" => "Chefe de Servi&#231;o de Pneumologia&#46; Coordenador do Servi&#231;o de Pneumologia do Hospital de Santa Maria&#44; Lisboa&#46; Assistente Convidado da Faculdade de Medicina de Lisboa&#46; Portugal"
            "etiqueta" => "<span class="elsevierStyleSup">2</span>"
            "identificador" => "aff0005"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "en" => array:1 [
        "titulo" => "Lung cancer in women&#58; A different entity&#63;"
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2006-03-26"
    "fechaAceptado" => "2006-05-03"
    "PalabrasClave" => array:2 [
      "pt" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palavras-chave"
          "identificador" => "xpalclavsec158853"
          "palabras" => array:4 [
            0 => "Cancro do pulm&#227;o"
            1 => "epidemiologia"
            2 => "biologia molecular"
            3 => "mulher"
          ]
        ]
      ]
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Key-words"
          "identificador" => "xpalclavsec158852"
          "palabras" => array:4 [
            0 => "Lung cancer"
            1 => "epidemiology"
            2 => "molecular biology"
            3 => "women"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "pt" => array:2 [
        "titulo" => "Resumo"
        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Nos pa&#237;ses desenvolvidos&#44; o cancro do pulm&#227;o tem vindo a tornar-se uma verdadeira epidemia e uma das principais causas de morte por neoplasias malignas na mulher&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Embora controverso&#44; &#233; prov&#225;vel que a mulher apresente maior susceptibilidade para o cancro do pulm&#227;o do que o homem&#44; estando a decorrer estudos de epidemiologia molecular e gen&#233;tica para a comprovar&#46; Apontam-se especificidades no que se refere &#224; biologia&#44; &#224; hist&#243;ria natural&#44; &#224; histopatologia&#44; &#224; resposta &#224; terap&#234;utica e ao progn&#243;stico do cancro do pulm&#227;o na mulher&#44; factos ainda n&#227;o completamente esclarecidos e&#44; em alguns aspectos&#44; n&#227;o consensuais&#44; havendo necessidade de se implementarem estudos prospectivos alargados para compara&#231;&#227;o dessas diferen&#231;as entre os dois sexos&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">At&#233; &#224; data&#44; na pr&#225;tica cl&#237;nica&#44; s&#243; existe uma &#225;rea em que o determinante sexo poder&#225; ser um factor a con siderar no manejo terap&#234;utico do cancro do pulm&#227;o&#44; que diz respeito ao valor do gefitinib e do erlotinib na inibi&#231;&#227;o dos receptores dos factores de crescimento epiderm&#243;ide&#44; em que estes produtos s&#227;o claramente mais ben&#233;ficos em mulheres n&#227;o fumadoras&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Dado o melhor progn&#243;stico do cancro do pulm&#227;o nas mulheres&#44; &#233; recomendado que os futuros protocolos de investiga&#231;&#227;o terap&#234;utica incluam uma estratifica&#231;&#227;o em fun&#231;&#227;o do sexo&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Na mulher&#44; tal como no homem&#44; a preven&#231;&#227;o do cancro do pulm&#227;o &#233; uma medida de sa&#250;de p&#250;blica priorit&#225;ria&#44; tendo como objectivo obrigat&#243;rio a luta contra o tabaco&#44; o seu factor etiol&#243;gico <span class="elsevierStyleItalic">major</span>&#46;</p>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Lung cancer is becoming a real epidemic in developed countries and one of the main causes of cancer death in women&#46;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Although it is controversial to state&#44; it is probable that women are more susceptible to lung cancer than men&#46; Molecular and genetic epidemiology studies are underway to prove this statement&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Several biological factors&#44; such as family history&#44; histopathology&#44; response to treatment and the prognosis for lung cancer in women have a bearing on the case&#46; While these are not completely clear or consensual&#44; there is a need for wide-ranging prospective studies which compare the differences between males and females&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Until now&#44; there has only been one area in which gender could impact on the therapeutic management of lung cancer&#58; the role of gefitinib and erlotinib in inhibiting the epidermal growth factor receptors&#44; since these products are clearly of more benefit to female non-smokers&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Given that women have a better lung cancer prognosis&#44; it is recommended that future research protocols include stratification on gender&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Prevention of lung cancer in both women and men is a priority public health concern&#46; A mandatory aim of this is the fight against smoking&#44; the largest aetiological factor of lung cancer</p>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "1"
        "nota" => "<p class="elsevierStyleNotepara">Texto apresentado em parte no &#8220;39&#46;&#176; Curso de Pneumologia para P&#243;s-Graduados&#8221; &#40;Universidade Cat&#243;lica&#44; Lisboa&#44; Mar&#231;o de 2006&#41;&#44; na sess&#227;o &#8220;Cancro do pulm&#227;o na mulher&#8221;&#46;</p>"
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Bibliografia"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:65 [
            0 => array:3 [
              "identificador" => "bib1"
              "etiqueta" => "1&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Determinants of improved outcome in small-cell lung cancer&#58; an analysis of the 2 580-patients Southwest Oncology Group database"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "K&#46;S&#46; Albain"
                            1 => "J&#46;L&#46; Crowley"
                            2 => "M&#46; LeBlanc"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Am J Clin Oncol"
                        "fecha" => "1990"
                        "volumen" => "8"
                        "paginaInicial" => "1563"
                        "paginaFinal" => "1574"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib2"
              "etiqueta" => "2&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology of lung cancer&#58; looking to the future"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46;J&#46; Alberg"
                            1 => "M&#46;V&#46; Brock"
                            2 => "J&#46;M&#46; Samet"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2005.10.462"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2005"
                        "volumen" => "23"
                        "paginaInicial" => "3175"
                        "paginaFinal" => "3185"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15886304"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib3"
              "etiqueta" => "3&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Combined analysis of molecular and clinical predictors of gefitinib activity in advanced non-small cell lung cancer&#58; epidermal growth factor receptor mutations do not tell the whole story"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46; Argiris"
                            1 => "T&#46; Hensing"
                            2 => "A&#46; Yeldandi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Thorac Oncol"
                        "fecha" => "2006"
                        "volumen" => "1"
                        "paginaInicial" => "52"
                        "paginaFinal" => "60"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17409827"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib4"
              "etiqueta" => "4&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lung cancer rates in men and women with comparable histories of smoking"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "C&#46; Bain"
                            1 => "D&#46; Feskanich"
                            2 => "F&#46;E&#46; Speizer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Natl Cancer Inst"
                        "fecha" => "2004"
                        "volumen" => "96"
                        "paginaInicial" => "826"
                        "paginaFinal" => "834"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15173266"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib5"
              "etiqueta" => "5&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Environmental tobacco smoke&#44; genetic susceptibility and risk of lung cancer in non-smoking women"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "W&#46;P&#46; Bennett"
                            1 => "M&#46;C&#46;R&#46; Alavanja"
                            2 => "B&#46; Blomeke"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Natl Cancer Inst"
                        "fecha" => "1999"
                        "volumen" => "91"
                        "paginaInicial" => "2009"
                        "paginaFinal" => "2014"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10580025"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib6"
              "etiqueta" => "6&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gender differences in quit rates folowing smoking cessation with combination nicotine therapy&#58; influence of baseline smoking behavior"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46; Bohadana"
                            1 => "F&#46; Nilsson"
                            2 => "T&#46; Rasmussen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1080/1462220021000060482"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nicotine Tob Res"
                        "fecha" => "2003"
                        "volumen" => "5"
                        "paginaInicial" => "111"
                        "paginaFinal" => "116"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12745512"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib7"
              "etiqueta" => "7&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lung cancer mortality in European women&#58; recent trends and perspectives"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "C&#46; Bosetti"
                            1 => "F&#46; Levi"
                            2 => "F&#46; Lucchini"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/annonc/mdi313"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Oncol"
                        "fecha" => "2005"
                        "volumen" => "16"
                        "paginaInicial" => "1597"
                        "paginaFinal" => "1604"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16014639"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib8"
              "etiqueta" => "8&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Direc&#231;&#227;o Geral da Sa&#250;de&#46; Plano Nacional de Sa&#250;de 2004-2010&#44; Volume II &#8211; Orienta&#231;&#245;es Estrat&#233;gicas&#44; Lisboa&#44; DGS&#44; 2004&#46;"
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib9"
              "etiqueta" => "9&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Direc&#231;&#227;o-Geral da Sa&#250;de&#46; Elementos Estat&#237;sticos&#58; Informa&#231;&#227;o Geral&#46; Sa&#250;de&#47;2003&#46; Lisboa&#44; DGS&#44; 2005&#46;"
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib10"
              "etiqueta" => "10&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Doll R&#46; Cancers weakly related to smoking&#46; <span class="elsevierStyleItalic">In</span> Doll R&#44; Crofton J &#40;eds&#41;&#46; Tobacco and Health&#46; British Medical Bulletin 1996&#59; 52&#40;1&#41;&#58;35-49&#46;"
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib11"
              "etiqueta" => "11&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gender differences in genetic susceptibility for lung cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "C&#46;M&#46; Dresler"
                            1 => "C&#46; Fratelli"
                            2 => "J&#46; Babb"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Lung Cancer"
                        "fecha" => "2000"
                        "volumen" => "30"
                        "paginaInicial" => "156"
                        "paginaFinal" => "160"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib12"
              "etiqueta" => "12&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Women and lung cancer&#58; potencial mechanisms of greater susceptibility to tobacco smoke"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C&#46;M&#46; Dresler"
                            1 => "E&#46;R&#46; Gritz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur Respir Mon"
                        "fecha" => "2003"
                        "volumen" => "25"
                        "paginaInicial" => "146"
                        "paginaFinal" => "151"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib13"
              "etiqueta" => "13&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Distributions of smokers by stage&#58; international comparison and association with smoking prevalence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46;-F&#46; Etter"
                            1 => "T&#46;V&#46; Perneger"
                            2 => "A&#46; Ronchi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1006/pmed.1997.0179"
                      "Revista" => array:6 [
                        "tituloSerie" => "Prev Med"
                        "fecha" => "1997"
                        "volumen" => "26"
                        "paginaInicial" => "580"
                        "paginaFinal" => "585"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9245682"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib14"
              "etiqueta" => "14&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lung cancer in women&#46; Analysis of the National Surveillance&#44; Epidemiology&#44; and End Results database"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46;B&#46; Fu"
                            1 => "Y&#46; Kau"
                            2 => "R&#46;K&#46; Severson"
                            3 => "G&#46;P&#46; Kalemkerian"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.127.3.768"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2005"
                        "volumen" => "127"
                        "paginaInicial" => "768"
                        "paginaFinal" => "777"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15764756"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib15"
              "etiqueta" => "15&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hormone replacement therapy is associated with decrease survival in women with lung cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46;K&#46; Ganti"
                            1 => "A&#46;E&#46; Sahmoun"
                            2 => "A&#46;W&#46; Panwalker"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2005.02.9827"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2006"
                        "volumen" => "24"
                        "paginaInicial" => "59"
                        "paginaFinal" => "63"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16314616"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib16"
              "etiqueta" => "16&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tobacco smoke carcinogens and lung cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "S&#46;S&#46; Hecht"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J Natl Cancer Inst"
                        "fecha" => "1999"
                        "volumen" => "91"
                        "numero" => "14"
                        "paginaInicial" => "1194"
                        "paginaFinal" => "1210"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10413421"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib17"
              "etiqueta" => "17&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "HPV positive bronchopulmonary carcinomas in women with previous high-grade cervical intraepitelial neoplasia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "E&#46;M&#46; Henning"
                            1 => "Z&#46; Suo"
                            2 => "F&#46; Karlsen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Oncol"
                        "fecha" => "1999"
                        "volumen" => "38"
                        "paginaInicial" => "639"
                        "paginaFinal" => "647"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10427955"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib18"
              "etiqueta" => "18&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Women&#39;s susceptibility to tobacco carcinogens"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C&#46;I&#46; Henschke"
                            1 => "O&#46;S&#46; Miettinen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Lung Cancer"
                        "fecha" => "2004"
                        "volumen" => "43"
                        "paginaInicial" => "1"
                        "paginaFinal" => "5"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14698531"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib19"
              "etiqueta" => "19&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Non-smoking wives of heavy smokers have a higher risk of lung cancer&#58; a study from Japan"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "T&#46; Hirayama"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Br Med J"
                        "fecha" => "1981"
                        "volumen" => "282"
                        "paginaInicial" => "183"
                        "paginaFinal" => "185"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib20"
              "etiqueta" => "20&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Role of biomarkers for ealy detection of lung cancer and chemoprevention"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "F&#46;R&#46; Hirsch"
                            1 => "D&#46;T&#46; Merrick"
                            2 => "W&#46;A&#46; Franklin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2002"
                        "volumen" => "19"
                        "paginaInicial" => "1151"
                        "paginaFinal" => "1158"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12108871"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib21"
              "etiqueta" => "21&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "IARC Technical Publications N&#46;&#176; 38&#44; Lyon 2002&#46;"
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib22"
              "etiqueta" => "22&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "INCP&#46; A situa&#231;&#227;o da sa&#250;de em Portugal em rela&#231;&#227;o a outros pa&#237;ses europeus&#46; Actualiza&#231;&#227;o e estudo comparativo no &#226;mbito do CINDI-Portugal&#46; Instituto Nacional de Cardiologia Preventiva&#44; 2002&#44; p&#46; 46&#46;"
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib23"
              "etiqueta" => "23&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidermal growth factor receptor mutations in non-small-cell lung cancer&#58; implications for treatment and tumor biology"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "P&#46;A&#46; J&#228;nne"
                            1 => "J&#46;A&#46; Engelman"
                            2 => "Johnson BE"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2005.09.985"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2005"
                        "volumen" => "23"
                        "numero" => "14"
                        "paginaInicial" => "3227"
                        "paginaFinal" => "3234"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15886310"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib24"
              "etiqueta" => "24&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lung cancer rates convergence in young men and women in the United States&#58; analysis by birth cohort and histologic type"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46; Jemal"
                            1 => "W&#46;D&#46; Travis"
                            2 => "R&#46;E&#46; Tarone"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/ijc.11020"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Cancer"
                        "fecha" => "2003"
                        "volumen" => "105"
                        "paginaInicial" => "101"
                        "paginaFinal" => "107"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12672038"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib25"
              "etiqueta" => "25&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Patterns of lung cancer mortality in 23 countries&#58; applications of the aged-period-cohort model"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Y&#46;-P&#46; Liaw"
                            1 => "Y&#46;-C&#46; Huang"
                            2 => "G&#46;-W&#46; Lien"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1471-2458-5-49"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMC Public Health"
                        "fecha" => "2005"
                        "volumen" => "5"
                        "numero" => "22"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15904514"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib26"
              "etiqueta" => "26&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "T&#46;J&#46; Lynch"
                            1 => "D&#46;W&#46; Bell"
                            2 => "R&#46; Sordella"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa040938"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2004"
                        "volumen" => "350"
                        "paginaInicial" => "2129"
                        "paginaFinal" => "2139"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15118073"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib27"
              "etiqueta" => "27&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Women and small cell lung cancer&#58; social characteristics&#44; medical history&#44; management and survival&#46; A retrospective study of all the male and female cases diagnosed in Bas-Rhin &#40;Eastern France&#41; between 1981 and 1994"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "B&#46; Mennecier"
                            1 => "M&#46;P&#46; Lebitasy"
                            2 => "L&#46; Moreau"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Lung Cancer"
                        "fecha" => "2003"
                        "volumen" => "42"
                        "paginaInicial" => "141"
                        "paginaFinal" => "152"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14568681"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib28"
              "etiqueta" => "28&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intake of specific caretinoids and risk of lung cancer in two prospective US cohorts"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "D&#46;S&#46; Michaud"
                            1 => "D&#46; Feskanich"
                            2 => "E&#46;D&#46; Rimm"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Clin Nutr"
                        "fecha" => "2000"
                        "volumen" => "72"
                        "paginaInicial" => "990"
                        "paginaFinal" => "997"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11010942"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib29"
              "etiqueta" => "29&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lung cancer in women&#46; Sex-associated differences in survival of patients undergoing resection for lung cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "H&#46; Minami"
                            1 => "M&#46; Yoshimura"
                            2 => "Y&#46; Miyamoto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2000"
                        "volumen" => "118"
                        "paginaInicial" => "1603"
                        "paginaFinal" => "1609"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11115446"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib30"
              "etiqueta" => "30&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sex differences in lung CYP1A1 expression and DNA adducts levels among lung cancer patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46; Mollerup"
                            1 => "D&#46; Ryberg"
                            2 => "A&#46; Hewer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Cancer Res"
                        "fecha" => "1999"
                        "volumen" => "59"
                        "paginaInicial" => "3317"
                        "paginaFinal" => "3320"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10416585"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib31"
              "etiqueta" => "31&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Implications and prognostic value of K-ras mutations for early-stage lung cancr in women"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "H&#46;H&#46; Nelson"
                            1 => "D&#46;C&#46; Christiani"
                            2 => "E&#46;J&#46; Mark"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Natl Cancer Inst &#40;Bethesda&#41;"
                        "fecha" => "1999"
                        "volumen" => "91"
                        "paginaInicial" => "2032"
                        "paginaFinal" => "2038"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib32"
              "etiqueta" => "32&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer&#58; a phase II study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "S&#46; Niho"
                            1 => "K&#46; Kubota"
                            2 => "K&#46; Goto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2005.02.5825"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2006"
                        "volumen" => "24"
                        "paginaInicial" => "64"
                        "paginaFinal" => "69"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16382114"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib33"
              "etiqueta" => "33&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "EGFR mutations in lung cancer&#58; correlations with clinical responce to gefitinib therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "J&#46;G&#46; Paez"
                            1 => "P&#46;A&#46; Janne"
                            2 => "J&#46;C&#46; Lee"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1126/science.1099314"
                      "Revista" => array:6 [
                        "tituloSerie" => "Science"
                        "fecha" => "2004"
                        "volumen" => "304"
                        "paginaInicial" => "1497"
                        "paginaFinal" => "1500"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15118125"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib34"
              "etiqueta" => "34&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lung cancer in women"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46;D&#46; Patel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2005.11.486"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2005"
                        "volumen" => "23"
                        "paginaInicial" => "3212"
                        "paginaFinal" => "3218"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15886308"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib35"
              "etiqueta" => "35&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lung cancer in women&#58; a contemporary epidemic"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46;D&#46; Patel"
                            1 => "P&#46;B&#46; Bach"
                            2 => "M&#46;G&#46; Kris"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.291.14.1763"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "2004"
                        "volumen" => "291"
                        "paginaInicial" => "1763"
                        "paginaFinal" => "1768"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15082704"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib36"
              "etiqueta" => "36&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Le cancer bronchique chez la femme"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "E&#46; Quoix"
                            1 => "B&#46; Mennecier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Mal Respir"
                        "fecha" => "2005"
                        "volumen" => "22"
                        "numero" => "8"
                        "paginaInicial" => "S55"
                        "paginaFinal" => "S62"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib37"
              "etiqueta" => "37&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lung cancer in women&#58; age&#44; smoking&#44; histology&#44; performance status&#44; stage&#44; initial treatment and survival&#46; Population-based study of 20 561 cases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "E&#46; Radzikowska"
                            1 => "P&#46; Glaz"
                            2 => "K&#46; Roszkowski"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Oncol"
                        "fecha" => "2002"
                        "volumen" => "13"
                        "paginaInicial" => "1087"
                        "paginaFinal" => "1093"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12176788"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib38"
              "etiqueta" => "38&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Ries LAG&#44; Kosary CL&#44; Hankey BF&#44; <span class="elsevierStyleItalic">et al</span>&#46; SEER Cancer Statistics Review&#44; 1973-1993&#58; Tables and Graphics&#46; Bethesda &#40;MD&#41;&#58; NCI&#44; 1996&#46;"
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib39"
              "etiqueta" => "39&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Are female smokers at higher risk for lung cancer than male smokers&#63; A case-control analysis by histologic type"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "H&#46;A&#46; Risch"
                            1 => "G&#46;R&#46; Howe"
                            2 => "M&#46; Jain"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Epidemiol"
                        "fecha" => "1993"
                        "volumen" => "138"
                        "paginaInicial" => "281"
                        "paginaFinal" => "293"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8395141"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib40"
              "etiqueta" => "40&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gender and lung cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;P&#46; Rivera"
                            1 => "D&#46;E&#46; Stover"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ccm.2004.01.006"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Chest Med"
                        "fecha" => "2004"
                        "volumen" => "25"
                        "paginaInicial" => "391"
                        "paginaFinal" => "400"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15099898"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib41"
              "etiqueta" => "41&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Factors predicting severe radiation pneumonitis in patients receiving definitive chemoradiation for lung cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "T&#46;J&#46; Robnett"
                            1 => "M&#46; Machtay"
                            2 => "E&#46;F&#46; Vines"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Radiat Oncol Biol Phys"
                        "fecha" => "2000"
                        "volumen" => "48"
                        "paginaInicial" => "89"
                        "paginaFinal" => "94"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10924976"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib42"
              "etiqueta" => "42&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Familial risk of lung cancer among nonsmokers and their relatives"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46;G&#46; Schwartz"
                            1 => "P&#46; Yang"
                            2 => "G&#46;M&#46; Swanson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Am J Epidemiol"
                        "fecha" => "1996"
                        "volumen" => "14"
                        "paginaInicial" => "554"
                        "paginaFinal" => "562"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib43"
              "etiqueta" => "43&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "SEER&#46; SEER incidence and mortality age-adjusted rates for lung cancer&#46; &#91;<span class="elsevierStyleItalic">on line database</span>&#93;&#44; Bethesda&#44; MD&#44; National Cancer Institute &#40;<a class="elsevierStyleInterRef" href="http://canque.seer.cancer.gov/cgi-bin/">http&#58;&#47;&#47;canque&#46;seer&#46;cancer&#46;gov&#47;cgi-bin&#47;</a>&#44; 2003&#41;&#46;"
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib44"
              "etiqueta" => "44&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Sherman NL&#44; Albain KS&#46; Sex differences in lung cancer outcome&#46; ASCO 2005 Educational Book&#44; 622-7&#46;"
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib45"
              "etiqueta" => "45&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Molecular epidemiology and the genetics of environmental cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "P&#46;G&#46; Shields"
                            1 => "C&#46;C&#46; Harris"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "1991"
                        "volumen" => "266"
                        "paginaInicial" => "681"
                        "paginaFinal" => "687"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2072479"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib46"
              "etiqueta" => "46&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Skuladottir H&#44; Olsen JH&#46; Epidemiology of lung cancer&#46; <span class="elsevierStyleItalic">In</span> Spiro SG &#40;ed&#41;&#46; Lung Cancer&#46; Eur Respir Mon 2001&#59; 17&#58;1-12&#46;"
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib47"
              "etiqueta" => "47&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Sotto-Mayor R&#46; Dados Hist&#243;ricos para o Estudo do Cancro do Pulm&#227;o&#46; <span class="elsevierStyleItalic">In</span> Sotto-Mayor R&#44; Teixeira E&#44; Ma&#231;anita J &#40;eds&#41;&#46; Oncologia Pneumol&#243;gica&#58; Temas de Actualiza&#231;&#227;o&#46; Lisboa&#44; Permanyer Portugal&#44; 1999&#44; pp&#46; 3-12&#46;"
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib48"
              "etiqueta" => "48&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tabaco e gen&#233;tica"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46; Sotto-Mayor"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Port Pneumol"
                        "fecha" => "2004"
                        "volumen" => "X"
                        "paginaInicial" => "S67"
                        "paginaFinal" => "S78"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib49"
              "etiqueta" => "49&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Factores de progn&#243;stico no cancro do pulm&#227;o&#58; algumas notas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46; Sotto-Mayor"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Port Pneumol"
                        "fecha" => "2005"
                        "volumen" => "XI"
                        "paginaInicial" => "S99"
                        "paginaFinal" => "S103"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib50"
              "etiqueta" => "50&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prognostic factors in small-cell carcinoma of the lung&#58; an analysis of 1 521 patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "D&#46; Spiegelman"
                            1 => "L&#46;H&#46; Maurer"
                            2 => "J&#46;H&#46; Ware"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/jco.1989.7.3.344"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "1989"
                        "volumen" => "7"
                        "paginaInicial" => "344"
                        "paginaFinal" => "354"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2537384"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib51"
              "etiqueta" => "51&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Human nonsmall cell lung tumors and cells derived from normal lung express both estrogen receptor &#945; and &#946; and show biological responses to estrogen"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "L&#46;P&#46; Stabile"
                            1 => "G&#46; Davis"
                            2 => "C&#46;T&#46; Gubish"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Cancer Res"
                        "fecha" => "2002"
                        "volumen" => "62"
                        "paginaInicial" => "2141"
                        "paginaFinal" => "2150"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11929836"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib52"
              "etiqueta" => "52&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Environmental tobacco smoke and lung cancer risk in nonsmoking women"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "H&#46;G&#46; Stockwell"
                            1 => "A&#46;L&#46; Goldman"
                            2 => "G&#46;H&#46; Lyman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Natl Cancer Inst"
                        "fecha" => "1992"
                        "volumen" => "84"
                        "paginaInicial" => "1417"
                        "paginaFinal" => "1422"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1512793"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib53"
              "etiqueta" => "53&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Re&#58; Endocrine factors and adenocarcinoma of lung in women"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "E&#46; Taioli"
                            1 => "E&#46;L&#46; Wynder"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Natl Cancer Inst"
                        "fecha" => "1994"
                        "volumen" => "86"
                        "paginaInicial" => "869"
                        "paginaFinal" => "870"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8182770"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib54"
              "etiqueta" => "54&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lung cancer in women&#46; Emerging differences in epidemiology&#44; biology&#44; and therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "L&#46; Thomas"
                            1 => "L&#46;A&#46; Doyle"
                            2 => "M&#46;J&#46; Edelman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.128.1.370"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2005"
                        "volumen" => "128"
                        "paginaInicial" => "370"
                        "paginaFinal" => "381"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16002959"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib55"
              "etiqueta" => "55&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Histological Typing of Lung and Pleural tumours&#46; World Health Organization"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "In collaboration with L&#46;H&#46; Sobin and Pathologists of 14 Countries"
                          "etal" => false
                          "autores" => array:5 [
                            0 => "W&#46;D&#46; Travis"
                            1 => "T&#46;V&#46; Colby"
                            2 => "B&#46; Corrin"
                            3 => "Y&#46; Shimosato"
                            4 => "E&#46; Brambilla"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:5 [
                        "edicion" => "Third Edition"
                        "titulo" => "International Histological Classification of Tumours"
                        "fecha" => "1999"
                        "editorial" => "Springer-Verlag"
                        "editorialLocalizacion" => "Berlin"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib56"
              "etiqueta" => "56&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "US Department of Health and Human Services&#46; Women and smoking&#58; a report of the Surgeon General&#46; Washington&#44; DC&#44; US Department of Health and Human Services&#44; Public Health Service&#44; Centers for Disease Control and Prevention&#44; 2001&#46;"
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib57"
              "etiqueta" => "57&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "US Department of Health and Human Services&#46; The health consequences of smoking&#58; a report of the Surgeon General&#46; Washington&#44; DC&#44; US Department of Health and Human Services&#44; Public Health Service&#44; Centers for Disease Control and Prevention&#44; 2004&#46;"
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib58"
              "etiqueta" => "58&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Wald NJ&#44; Hackshaw AK&#46; Cigarette smoking&#58; an epidemiological overview&#46; <span class="elsevierStyleItalic">In</span> Doll R&#44; Crofton J &#40;eds&#41;&#46; Tobacco and health&#46; British Medical Bulletin 1996&#59; 52&#40;1&#41;&#58;3-11&#46;"
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib59"
              "etiqueta" => "59&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk&#58; a molecular epidemiological study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Q&#46; Weis"
                            1 => "L&#46; Cheng"
                            2 => "C&#46;I&#46; Amos"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Natl Cancer Inst &#40;Bethesda&#41;"
                        "fecha" => "2000"
                        "volumen" => "92"
                        "paginaInicial" => "1764"
                        "paginaFinal" => "1772"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib60"
              "etiqueta" => "60&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Human papilloma-virus infection is not associated with bronchial carcinoma&#58; evaluation by <span class="elsevierStyleItalic">in situ</span> hybridization and the polymerase chain reaction"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46; Welt"
                            1 => "M&#46; Hummel"
                            2 => "G&#46; Niedobitek"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/(SICI)1096-9896(199703)181:3<276::AID-PATH738>3.0.CO;2-L"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pathol"
                        "fecha" => "1997"
                        "volumen" => "181"
                        "paginaInicial" => "276"
                        "paginaFinal" => "280"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9155712"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib61"
              "etiqueta" => "61&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Recursive partitioning analysis of 1999 Radiation Therapy Oncology Group &#40;RTOG&#41; patients with locally-advanced non-small cell lung cancer &#40;LA-NSCLC&#41;&#59; Identification of five groups with different survival"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "M&#46; Werner-Wasik"
                            1 => "C&#46; Scott"
                            2 => "J&#46;D&#46; Cox"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Radiat Oncol Biol Phys"
                        "fecha" => "2000"
                        "volumen" => "48"
                        "paginaInicial" => "1475"
                        "paginaFinal" => "1482"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11121651"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib62"
              "etiqueta" => "62&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "World Cancer Research Fund&#47;American Institute for Cancer Reseach&#58; Food&#44; Nutrition and the Prevention of Cancer&#46; A Global Perspective&#46; Washington &#40;DC&#41;&#58; American Institute for Cancer Research&#44; 1997&#59; 37&#46;"
                ]
              ]
            ]
            62 => array:3 [
              "identificador" => "bib63"
              "etiqueta" => "63&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "World Health Organization&#46; Gender in lung cancer and smoking research&#46; WHO&#44; Department of Gender&#44; Women and Health &#40;GWH&#41;&#44; Geneva&#44; 2004&#46; 64&#46; van Zandwijk N&#46; Aetiology and prevention of lung cancer&#46; <span class="elsevierStyleItalic">In</span> Spiro SG &#40;ed&#41;&#46; Lung Cancer&#46; Eur Respir Mon 2001&#59; 17&#58;13-33&#46;"
                ]
              ]
            ]
            63 => array:3 [
              "identificador" => "bib64"
              "etiqueta" => "65&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Differences in lung cancer risk between men and women&#58; Examination of the evidence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "E&#46;A&#46; Zang"
                            1 => "El&#46; Wynder"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Natl Cancer Inst"
                        "fecha" => "1996"
                        "volumen" => "88"
                        "paginaInicial" => "183"
                        "paginaFinal" => "192"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8632492"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            64 => array:3 [
              "identificador" => "bib65"
              "etiqueta" => "66&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Based casecontrol study of lung cancer and green tea consumption among women living in Shanghai China"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "L&#46; Zhong"
                            1 => "M&#46;S&#46; Goldberg"
                            2 => "Y&#46;T&#46; Gao"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Epidemiology"
                        "fecha" => "2001"
                        "volumen" => "12"
                        "paginaInicial" => "695"
                        "paginaFinal" => "700"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11679799"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "pt"
  "url" => "/21735115/0000001200000005/v1_201305151428/S2173511506704201/v1_201305151428/pt/main.assets"
  "Apartado" => array:4 [
    "identificador" => "9551"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Review Article&#47;Artigo de Revis&#227;o"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/21735115/0000001200000005/v1_201305151428/S2173511506704201/v1_201305151428/pt/main.pdf?idApp=UINPBA00004E&text.app=https://journalpulmonology.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173511506704201?idApp=UINPBA00004E"
]
Share
Journal Information
Vol. 12. Issue 5.
Pages 545-561 (September - October 2006)
Share
Share
Download PDF
More article options
Vol. 12. Issue 5.
Pages 545-561 (September - October 2006)
Full text access
Cancro do pulmão na mulher: Uma entidade diferente?
Lung cancer in women: A different entity?
Visits
916
Renato Sotto-Mayor2
2 Chefe de Serviço de Pneumologia. Coordenador do Serviço de Pneumologia do Hospital de Santa Maria, Lisboa. Assistente Convidado da Faculdade de Medicina de Lisboa. Portugal
This item has received
Article information
Resumo

Nos países desenvolvidos, o cancro do pulmão tem vindo a tornar-se uma verdadeira epidemia e uma das principais causas de morte por neoplasias malignas na mulher.

Embora controverso, é provável que a mulher apresente maior susceptibilidade para o cancro do pulmão do que o homem, estando a decorrer estudos de epidemiologia molecular e genética para a comprovar. Apontam-se especificidades no que se refere à biologia, à história natural, à histopatologia, à resposta à terapêutica e ao prognóstico do cancro do pulmão na mulher, factos ainda não completamente esclarecidos e, em alguns aspectos, não consensuais, havendo necessidade de se implementarem estudos prospectivos alargados para comparação dessas diferenças entre os dois sexos.

Até à data, na prática clínica, só existe uma área em que o determinante sexo poderá ser um factor a con siderar no manejo terapêutico do cancro do pulmão, que diz respeito ao valor do gefitinib e do erlotinib na inibição dos receptores dos factores de crescimento epidermóide, em que estes produtos são claramente mais benéficos em mulheres não fumadoras.

Dado o melhor prognóstico do cancro do pulmão nas mulheres, é recomendado que os futuros protocolos de investigação terapêutica incluam uma estratificação em função do sexo.

Na mulher, tal como no homem, a prevenção do cancro do pulmão é uma medida de saúde pública prioritária, tendo como objectivo obrigatório a luta contra o tabaco, o seu factor etiológico major.

Palavras-chave:
Cancro do pulmão
epidemiologia
biologia molecular
mulher
Abstract

Lung cancer is becoming a real epidemic in developed countries and one of the main causes of cancer death in women.

Although it is controversial to state, it is probable that women are more susceptible to lung cancer than men. Molecular and genetic epidemiology studies are underway to prove this statement.

Several biological factors, such as family history, histopathology, response to treatment and the prognosis for lung cancer in women have a bearing on the case. While these are not completely clear or consensual, there is a need for wide-ranging prospective studies which compare the differences between males and females.

Until now, there has only been one area in which gender could impact on the therapeutic management of lung cancer: the role of gefitinib and erlotinib in inhibiting the epidermal growth factor receptors, since these products are clearly of more benefit to female non-smokers.

Given that women have a better lung cancer prognosis, it is recommended that future research protocols include stratification on gender.

Prevention of lung cancer in both women and men is a priority public health concern. A mandatory aim of this is the fight against smoking, the largest aetiological factor of lung cancer

Key-words:
Lung cancer
epidemiology
molecular biology
women
Full text is only aviable in PDF
Bibliografia
[1.]
K.S. Albain, J.L. Crowley, M. LeBlanc, et al.
Determinants of improved outcome in small-cell lung cancer: an analysis of the 2 580-patients Southwest Oncology Group database.
Am J Clin Oncol, 8 (1990), pp. 1563-1574
[2.]
A.J. Alberg, M.V. Brock, J.M. Samet.
Epidemiology of lung cancer: looking to the future.
J Clin Oncol, 23 (2005), pp. 3175-3185
[3.]
A. Argiris, T. Hensing, A. Yeldandi, et al.
Combined analysis of molecular and clinical predictors of gefitinib activity in advanced non-small cell lung cancer: epidermal growth factor receptor mutations do not tell the whole story.
J Thorac Oncol, 1 (2006), pp. 52-60
[4.]
C. Bain, D. Feskanich, F.E. Speizer, et al.
Lung cancer rates in men and women with comparable histories of smoking.
J Natl Cancer Inst, 96 (2004), pp. 826-834
[5.]
W.P. Bennett, M.C.R. Alavanja, B. Blomeke, et al.
Environmental tobacco smoke, genetic susceptibility and risk of lung cancer in non-smoking women.
J Natl Cancer Inst, 91 (1999), pp. 2009-2014
[6.]
A. Bohadana, F. Nilsson, T. Rasmussen.
Gender differences in quit rates folowing smoking cessation with combination nicotine therapy: influence of baseline smoking behavior.
Nicotine Tob Res, 5 (2003), pp. 111-116
[7.]
C. Bosetti, F. Levi, F. Lucchini, et al.
Lung cancer mortality in European women: recent trends and perspectives.
Ann Oncol, 16 (2005), pp. 1597-1604
[8.]
Direcção Geral da Saúde. Plano Nacional de Saúde 2004-2010, Volume II – Orientações Estratégicas, Lisboa, DGS, 2004.
[9.]
Direcção-Geral da Saúde. Elementos Estatísticos: Informação Geral. Saúde/2003. Lisboa, DGS, 2005.
[10.]
Doll R. Cancers weakly related to smoking. In Doll R, Crofton J (eds). Tobacco and Health. British Medical Bulletin 1996; 52(1):35-49.
[11.]
C.M. Dresler, C. Fratelli, J. Babb, et al.
Gender differences in genetic susceptibility for lung cancer.
Lung Cancer, 30 (2000), pp. 156-160
[12.]
C.M. Dresler, E.R. Gritz.
Women and lung cancer: potencial mechanisms of greater susceptibility to tobacco smoke.
Eur Respir Mon, 25 (2003), pp. 146-151
[13.]
J.-F. Etter, T.V. Perneger, A. Ronchi.
Distributions of smokers by stage: international comparison and association with smoking prevalence.
Prev Med, 26 (1997), pp. 580-585
[14.]
J.B. Fu, Y. Kau, R.K. Severson, G.P. Kalemkerian.
Lung cancer in women. Analysis of the National Surveillance, Epidemiology, and End Results database.
Chest, 127 (2005), pp. 768-777
[15.]
A.K. Ganti, A.E. Sahmoun, A.W. Panwalker, et al.
Hormone replacement therapy is associated with decrease survival in women with lung cancer.
J Clin Oncol, 24 (2006), pp. 59-63
[16.]
S.S. Hecht.
Tobacco smoke carcinogens and lung cancer.
J Natl Cancer Inst, 91 (1999), pp. 1194-1210
[17.]
E.M. Henning, Z. Suo, F. Karlsen, et al.
HPV positive bronchopulmonary carcinomas in women with previous high-grade cervical intraepitelial neoplasia.
Acta Oncol, 38 (1999), pp. 639-647
[18.]
C.I. Henschke, O.S. Miettinen.
Women's susceptibility to tobacco carcinogens.
Lung Cancer, 43 (2004), pp. 1-5
[19.]
T. Hirayama.
Non-smoking wives of heavy smokers have a higher risk of lung cancer: a study from Japan.
Br Med J, 282 (1981), pp. 183-185
[20.]
F.R. Hirsch, D.T. Merrick, W.A. Franklin.
Role of biomarkers for ealy detection of lung cancer and chemoprevention.
Eur Respir J, 19 (2002), pp. 1151-1158
[21.]
IARC Technical Publications N.° 38, Lyon 2002.
[22.]
INCP. A situação da saúde em Portugal em relação a outros países europeus. Actualização e estudo comparativo no âmbito do CINDI-Portugal. Instituto Nacional de Cardiologia Preventiva, 2002, p. 46.
[23.]
P.A. Jänne, J.A. Engelman, Johnson BE.
Epidermal growth factor receptor mutations in non-small-cell lung cancer: implications for treatment and tumor biology.
J Clin Oncol, 23 (2005), pp. 3227-3234
[24.]
A. Jemal, W.D. Travis, R.E. Tarone, et al.
Lung cancer rates convergence in young men and women in the United States: analysis by birth cohort and histologic type.
Int J Cancer, 105 (2003), pp. 101-107
[25.]
Y.-P. Liaw, Y.-C. Huang, G.-W. Lien.
Patterns of lung cancer mortality in 23 countries: applications of the aged-period-cohort model.
BMC Public Health, 5 (2005),
[26.]
T.J. Lynch, D.W. Bell, R. Sordella, et al.
Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.
N Engl J Med, 350 (2004), pp. 2129-2139
[27.]
B. Mennecier, M.P. Lebitasy, L. Moreau, et al.
Women and small cell lung cancer: social characteristics, medical history, management and survival. A retrospective study of all the male and female cases diagnosed in Bas-Rhin (Eastern France) between 1981 and 1994.
Lung Cancer, 42 (2003), pp. 141-152
[28.]
D.S. Michaud, D. Feskanich, E.D. Rimm, et al.
Intake of specific caretinoids and risk of lung cancer in two prospective US cohorts.
Am J Clin Nutr, 72 (2000), pp. 990-997
[29.]
H. Minami, M. Yoshimura, Y. Miyamoto, et al.
Lung cancer in women. Sex-associated differences in survival of patients undergoing resection for lung cancer.
Chest, 118 (2000), pp. 1603-1609
[30.]
S. Mollerup, D. Ryberg, A. Hewer.
Sex differences in lung CYP1A1 expression and DNA adducts levels among lung cancer patients.
Cancer Res, 59 (1999), pp. 3317-3320
[31.]
H.H. Nelson, D.C. Christiani, E.J. Mark, et al.
Implications and prognostic value of K-ras mutations for early-stage lung cancr in women.
J Natl Cancer Inst (Bethesda), 91 (1999), pp. 2032-2038
[32.]
S. Niho, K. Kubota, K. Goto, et al.
First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer: a phase II study.
J Clin Oncol, 24 (2006), pp. 64-69
[33.]
J.G. Paez, P.A. Janne, J.C. Lee, et al.
EGFR mutations in lung cancer: correlations with clinical responce to gefitinib therapy.
Science, 304 (2004), pp. 1497-1500
[34.]
J.D. Patel.
Lung cancer in women.
J Clin Oncol, 23 (2005), pp. 3212-3218
[35.]
J.D. Patel, P.B. Bach, M.G. Kris.
Lung cancer in women: a contemporary epidemic.
JAMA, 291 (2004), pp. 1763-1768
[36.]
E. Quoix, B. Mennecier.
Le cancer bronchique chez la femme.
Rev Mal Respir, 22 (2005), pp. S55-S62
[37.]
E. Radzikowska, P. Glaz, K. Roszkowski.
Lung cancer in women: age, smoking, histology, performance status, stage, initial treatment and survival. Population-based study of 20 561 cases.
Ann Oncol, 13 (2002), pp. 1087-1093
[38.]
Ries LAG, Kosary CL, Hankey BF, et al. SEER Cancer Statistics Review, 1973-1993: Tables and Graphics. Bethesda (MD): NCI, 1996.
[39.]
H.A. Risch, G.R. Howe, M. Jain, et al.
Are female smokers at higher risk for lung cancer than male smokers? A case-control analysis by histologic type.
Am J Epidemiol, 138 (1993), pp. 281-293
[40.]
M.P. Rivera, D.E. Stover.
Gender and lung cancer.
Clin Chest Med, 25 (2004), pp. 391-400
[41.]
T.J. Robnett, M. Machtay, E.F. Vines, et al.
Factors predicting severe radiation pneumonitis in patients receiving definitive chemoradiation for lung cancer.
Int J Radiat Oncol Biol Phys, 48 (2000), pp. 89-94
[42.]
A.G. Schwartz, P. Yang, G.M. Swanson.
Familial risk of lung cancer among nonsmokers and their relatives.
Am J Epidemiol, 14 (1996), pp. 554-562
[43.]
SEER. SEER incidence and mortality age-adjusted rates for lung cancer. [on line database], Bethesda, MD, National Cancer Institute (http://canque.seer.cancer.gov/cgi-bin/, 2003).
[44.]
Sherman NL, Albain KS. Sex differences in lung cancer outcome. ASCO 2005 Educational Book, 622-7.
[45.]
P.G. Shields, C.C. Harris.
Molecular epidemiology and the genetics of environmental cancer.
JAMA, 266 (1991), pp. 681-687
[46.]
Skuladottir H, Olsen JH. Epidemiology of lung cancer. In Spiro SG (ed). Lung Cancer. Eur Respir Mon 2001; 17:1-12.
[47.]
Sotto-Mayor R. Dados Históricos para o Estudo do Cancro do Pulmão. In Sotto-Mayor R, Teixeira E, Maçanita J (eds). Oncologia Pneumológica: Temas de Actualização. Lisboa, Permanyer Portugal, 1999, pp. 3-12.
[48.]
R. Sotto-Mayor.
Tabaco e genética.
Rev Port Pneumol, X (2004), pp. S67-S78
[49.]
R. Sotto-Mayor.
Factores de prognóstico no cancro do pulmão: algumas notas.
Rev Port Pneumol, XI (2005), pp. S99-S103
[50.]
D. Spiegelman, L.H. Maurer, J.H. Ware, et al.
Prognostic factors in small-cell carcinoma of the lung: an analysis of 1 521 patients.
J Clin Oncol, 7 (1989), pp. 344-354
[51.]
L.P. Stabile, G. Davis, C.T. Gubish, et al.
Human nonsmall cell lung tumors and cells derived from normal lung express both estrogen receptor α and β and show biological responses to estrogen.
Cancer Res, 62 (2002), pp. 2141-2150
[52.]
H.G. Stockwell, A.L. Goldman, G.H. Lyman.
Environmental tobacco smoke and lung cancer risk in nonsmoking women.
J Natl Cancer Inst, 84 (1992), pp. 1417-1422
[53.]
E. Taioli, E.L. Wynder.
Re: Endocrine factors and adenocarcinoma of lung in women.
J Natl Cancer Inst, 86 (1994), pp. 869-870
[54.]
L. Thomas, L.A. Doyle, M.J. Edelman.
Lung cancer in women. Emerging differences in epidemiology, biology, and therapy.
Chest, 128 (2005), pp. 370-381
[55.]
W.D. Travis, T.V. Colby, B. Corrin, Y. Shimosato, E. Brambilla, In collaboration with L.H. Sobin and Pathologists of 14 Countries.
Histological Typing of Lung and Pleural tumours. World Health Organization.
International Histological Classification of Tumours, Third Edition, Springer-Verlag, (1999),
[56.]
US Department of Health and Human Services. Women and smoking: a report of the Surgeon General. Washington, DC, US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, 2001.
[57.]
US Department of Health and Human Services. The health consequences of smoking: a report of the Surgeon General. Washington, DC, US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, 2004.
[58.]
Wald NJ, Hackshaw AK. Cigarette smoking: an epidemiological overview. In Doll R, Crofton J (eds). Tobacco and health. British Medical Bulletin 1996; 52(1):3-11.
[59.]
Q. Weis, L. Cheng, C.I. Amos, et al.
Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk: a molecular epidemiological study.
J Natl Cancer Inst (Bethesda), 92 (2000), pp. 1764-1772
[60.]
A. Welt, M. Hummel, G. Niedobitek, et al.
Human papilloma-virus infection is not associated with bronchial carcinoma: evaluation by in situ hybridization and the polymerase chain reaction.
[61.]
M. Werner-Wasik, C. Scott, J.D. Cox, et al.
Recursive partitioning analysis of 1999 Radiation Therapy Oncology Group (RTOG) patients with locally-advanced non-small cell lung cancer (LA-NSCLC); Identification of five groups with different survival.
Int J Radiat Oncol Biol Phys, 48 (2000), pp. 1475-1482
[62.]
World Cancer Research Fund/American Institute for Cancer Reseach: Food, Nutrition and the Prevention of Cancer. A Global Perspective. Washington (DC): American Institute for Cancer Research, 1997; 37.
[63.]
World Health Organization. Gender in lung cancer and smoking research. WHO, Department of Gender, Women and Health (GWH), Geneva, 2004. 64. van Zandwijk N. Aetiology and prevention of lung cancer. In Spiro SG (ed). Lung Cancer. Eur Respir Mon 2001; 17:13-33.
[65.]
E.A. Zang, El. Wynder.
Differences in lung cancer risk between men and women: Examination of the evidence.
J Natl Cancer Inst, 88 (1996), pp. 183-192
[66.]
L. Zhong, M.S. Goldberg, Y.T. Gao, et al.
Based casecontrol study of lung cancer and green tea consumption among women living in Shanghai China.
Epidemiology, 12 (2001), pp. 695-700

Texto apresentado em parte no “39.° Curso de Pneumologia para Pós-Graduados” (Universidade Católica, Lisboa, Março de 2006), na sessão “Cancro do pulmão na mulher”.

Copyright © 2006. Sociedade Portuguesa de Pneumologia
Download PDF
Pulmonology
Article options
Tools

Are you a health professional able to prescribe or dispense drugs?