Do genetic factors protect for early onset lung cancer? A case control study before the age of 50 years

246 patients with a primary, histologically or cytologically confirmed neoplasm, recruited from 2000 to 2003 in major lung clinics across Germany, were matched to 223 unrelated healthy controls. 11 single nucleotide polymorphisms of genes with reported associations to lung cancer have been genotyped.Genetic associations or gene-smoking interactions was found for GPX1(Pro200Leu) and EPHX1(His113Tyr). Carriers of the Leu-allele of GPX1(Pro200Leu) showed a significant risk reduction of OR = 0.6 (95% CI: 0.4–0.8, p = 0.002) in general and of OR = 0.3 (95% CI:0.1–0.8, p = 0.012) within heavy smokers. We could also find a risk decreasing genetic effect for His-carriers of EPHX1(His113Tyr) for moderate smokers (OR = 0.2, 95% CI:0.1–0.7, p = 0.012). Considered both variants together, a monotone decrease of the OR was found for smokers (OR of 0.20; 95% CI: 0.07–0.60) for each protective allele.Smoking is the most important risk factor for young lung cancer patients. However, this study provides some support for the T-Allel of GPX1(Pro200Leu) and the C-Allele of EPHX1(His113Tyr) to play a protective role in early onset lung cancer susceptibility.Lung cancer is the most common cause of death from cancer in the world. The estimated total number of cases is 1.2 million annually and is still increasing [1,2]. For men lung cancer mortality is declining in Germany since nearly a decade, whereas the incidence in women is increasing. However for men and women of age 50 or younger the incidence of lung cancer is low [1].The major cause of lung cancer is tobacco smoke, primarily of cigarettes, increasing the risk 15- to 30-fold. 90% of lung cancer cases can be attributed to a life long inhalation of tobacco smoke [1,3]. Additionally occupational (e.g. asbestos at workplace), environmental (e.g. passive smoking or ambient air pollution) and behavioral risk factors (e.g. diet) have been identified [1,2,4-14].The median age of onset is 66 years; about 5% to 10% of patients are younger tha