title: Familial risk of lung carcinoma in the Icelandic population.
abstract: BACKGROUND
  The dominant role of tobacco smoke as a causative factor in lung carcinoma is well established; however, an inherited predisposition may also be an important factor in the susceptibility to lung carcinoma.
  
  
  OBJECTIVE
  To investigate the contribution of genetic factors to the risk of developing lung carcinoma in the Icelandic population.
  
  
  METHODS
  Risk ratios (RRs) of lung carcinoma for first-, second-, and third-degree relatives of patients with lung carcinoma were estimated by linking records from the Icelandic Cancer Registry (ICR) of all 2756 patients diagnosed with lung carcinoma within the Icelandic population from January 1, 1955, to February 28, 2002, with an extensive genealogical database containing all living Icelanders and most of their ancestors since the settlement of Iceland. The RR for smoking was similarly estimated using a random population-based cohort of 10,541 smokers from the Reykjavik Heart Study who had smoked for more than 10 years. Of these smokers, 562 developed lung cancer based on the patients with lung cancer list from the ICR.
  
  
  METHODS
  Estimation of RRs of close and distant relatives of patients with lung carcinoma and comparison with RRs for close and distant relatives of smokers.
  
  
  RESULTS
  A familial factor for lung carcinoma was shown to extend beyond the nuclear family, as evidenced by significantly increased RR for first-degree relatives (for parents: RR, 2.69; 95% confidence interval [CI], 2.20-3.23; for siblings: RR, 2.02; 95% CI, 1.77-2.23; and for children: RR, 1.96; 95% CI, 1.53-2.39), second-degree relatives (for uncles/aunts: RR, 1.34; 95% CI, 1.15-1.49; and for nephews/nieces: RR, 1.28; 95% CI, 1.10-1.43), and third-degree relatives (for cousins: RR, 1.14; 95% CI, 1.05-1.22) of patients with lung carcinoma. This effect was stronger for relatives of patients with early-onset disease (age at onset < or =60 years) (for parents: RR, 3.48; 95% CI, 1.83-8.21; for siblings: RR, 3.30; 95% CI, 2.19-4.58; and for children: RR, 2.84; 95% CI, 1.34-7.21). The hypothesis that this increased risk is solely due to the effects of smoking was rejected for all relationships, except cousins and spouses, with a single-sided test of the RRs for lung carcinoma vs RRs for smoking.
  
  
  CONCLUSIONS
  These results underscore the importance of genetic predisposition in the development of lung carcinoma, with its strongest effect in patients with early-onset disease. However, tobacco smoke plays a dominant role in the pathogenesis of this disease, even among those individuals who are genetically predisposed to lung carcinoma.
authors.affiliation: Department of Medicine, Landspitali-University Hospital, Reykjavík, Iceland.
authors.forename: Steinn
authors.initials: S
authors.lastname: Jonsson
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Gudbjartsson
authors.forename: Hjortur H
authors.initials: HH
authors.lastname: Jonsson
authors.forename: Kristleifur
authors.initials: K
authors.lastname: Kristjansson
authors.forename: Sigurdur
authors.initials: S
authors.lastname: Arnason
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.forename: Helgi J
authors.initials: HJ
authors.lastname: Isaksson
authors.forename: Jonas
authors.initials: J
authors.lastname: Hallgrimsson
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gulcher
authors.forename: Laufey T
authors.initials: LT
authors.lastname: Amundadottir
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics; D000328:Adult; D018288:Carcinoma, Small Cell / Q000453:epidemiology / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D012042:Registries; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D014028:Tobacco Smoke Pollution
chemical_list: D014028:Tobacco Smoke Pollution