title: Evidence for a genetical contribution to non-smoking-related lung cancer.
abstract: BACKGROUND
  The majority of lung cancers are smoking-related, with environmental and genetical factors contributing. The interplay between environmental and genetical contributions in non-smoking-related lung cancers is less clear.
  
  
  METHODS
  We analysed a population-based computerised genealogy resource linked to a state-wide cancer registry of lung cancer cases (n=5544) for evidence of a genetical contribution to lung cancer predisposition in smoking (n=1747) and non-smoking cases (n=784). Statistical methods were used to test for significant excess relatedness of cases and estimate relative risk (RR) in close and distant relatives of lung cancer cases.
  
  
  RESULTS
  Significant excess relatedness was observed for all lung cancer cases (p<0.001) and for the subsets of smoking-related (p<0.001) and non-smoking-related (p<0.001) cases when all pairwise relationships were considered. Only the non-smoking-related subset of cases showed significant excess relatedness when close relationships were ignored (p=0.020). First-degree, second-degree, and fourth-degree relatives of non-smoking-related lung cancer cases had significantly elevated RR. An even higher elevated RR was observed for first-degree, second-degree, third-degree and fourth-degree relatives of smoking-related lung cancer cases.
  
  
  CONCLUSIONS
  Non-smoking-related lung cancer cases show significant excess relatedness for close and distant relationships, providing strong evidence for a genetical contribution as well as an environmental contribution. Significant excess relatedness for only close family relationships in all lung cancer cases and in only smoking-related lung cancer cases implies environmental contribution. Additionally, the highest RR for lung cancer was observed in the relatives of smoking-related lung cancer, suggesting predisposition gene carriers who smoke are at highest risk for lung cancer. Screening and gene identification should focus on high-risk pedigrees.
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Shamus R
authors.identifier: http://orcid.org/0000-0002-7958-3493
authors.initials: SR
authors.lastname: Carr
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA.
authors.forename: Wallace
authors.initials: W
authors.lastname: Akerley
authors.affiliation: Division of Public Health, Department of Family & Preventive Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA.
authors.forename: Mia
authors.initials: M
authors.lastname: Hashibe
authors.affiliation: Division of Genetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cannon-Albright
mesh_terms: D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D009017:Morbidity / Q000639:trends; D010375:Pedigree; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking; D014589:Utah / Q000453:epidemiology
keywords: Clinical Epidemiology; Lung Cancer