We genotyped blood samples from 432 lung cancer cases and 798 persons in a comparison group and examined the role of the GPX1 (Pro198Leu, rs1050450) polymorphism and interactions with external exposures in the development of lung cancer. The incidence rate ratio for lung cancer was 0.60 (95% confidence interval: 0.35-1.05) when homozygous carriers of the variant allele were compared with the homozygous carriers of the wild type, and the risk for lung cancer was significantly lower among participants carrying more variant alleles (p-trend=0.03). We found stronger associations between several smoking variables and alcohol intake and lung cancer risk among GPX1(TT) carriers than among GPX1(CC) and GPX1(CT) carriers.