Increased risk of lung cancer in individuals with a family history of the disease: A pooled analysis from the International Lung Cancer Consortium

Michele L. Coté, Mei Liu, Stefano Bonassi, Monica Neri, Ann G. Schwartz, David C. Christiani, Margaret R. Spitz, Joshua E. Muscat, Gad Rennert, Katja K. Aben, Angeline S. Andrew, Vladimir Bencko, Heike Bickeböller, Paolo Boffetta, Paul Brennan, Hermann Brenner, Eric J. Duell, Eleonora Fabianova, John K. Field, Lenka ForetovaSøren Friis, Curtis C. Harris, Ivana Holcatova, Yun Chul Hong, Dolores Isla, Vladimir Janout, Lambertus A. Kiemeney, Chikako Kiyohara, Qing Lan, Philip Lazarus, Jolanta Lissowska, Loic Le Marchand, Dana Mates, Keitaro Matsuo, Jose I. Mayordomo, John R. McLaughlin, Hal Morgenstern, Heiko Müeller, Irene Orlow, Bernard J. Park, Mila Pinchev, Olaide Y. Raji, Hedy S. Rennert, Peter Rudnai, Adeline Seow, Isabelle Stucker, Neonila Szeszenia-Dabrowska, M. Dawn Teare, Anne Tjønnelan, Donatella Ugolini, Henricus F.M. Van Der Heijden, Erich Wichmann, John K. Wiencke, Penella J. Woll, Ping Yang, David Zaridze, Zuo Feng Zhang, Carol J. Etzel, Rayjean J. Hung

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125 Scopus citations


Background and methods: Familial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology, relative type and ethnicity is not well described. This pooled analysis included 24 case-control studies in the International Lung Cancer Consortium. Each study collected age of onset/interview, gender, race/ethnicity, cigarette smoking, histology and first-degree family history of lung cancer. Data from 24,380 lung cancer cases and 23,305 healthy controls were analysed. Unconditional logistic regression models and generalised estimating equations were used to estimate odds ratios and 95% confidence intervals. Results: Individuals with a first-degree relative with lung cancer had a 1.51-fold increase in the risk of lung cancer, after adjustment for smoking and other potential confounders (95% CI: 1.39, 1.63). The association was strongest for those with a family history in a sibling, after adjustment (odds ratios (OR) = 1.82, 95% CI: 1.62, 2.05). No modifying effect by histologic type was found. Never smokers showed a lower association with positive familial history of lung cancer (OR = 1.25, 95% CI: 1.03, 1.52), slightly stronger for those with an affected sibling (OR = 1.44, 95% CI: 1.07, 1.93), after adjustment. Conclusions: The occurrence of lung cancer among never smokers and similar magnitudes of the effect of family history on lung cancer risk across histological types suggests familial aggregation of lung cancer is independent of those risks associated with cigarette smoking. While the role of genetic variation in the aetiology of lung cancer remains to be fully characterised, family history assessment is immediately available and those with a positive history represent a higher risk group.

Original languageEnglish (US)
Pages (from-to)1957-1968
Number of pages12
JournalEuropean Journal of Cancer
Issue number13
StatePublished - Sep 2012

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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