Smoking and the risk of lung cancer: susceptibility with GSTP1 polymorphisms

BACKGROUND: GSTP1 is a gene that helps detoxify foreign substances in the body. Functional polymorphisms of GSTP1 have been studied as risk factors for lung cancer. Past studies have compared the effect of the "at risk" polymorphism in two strata of smoking pack-years (usually defined by the median among controls). We examined the interaction between GSTP1 polymorphisms and cumulative exposure to smoking and their association with lung cancer risk. METHODS: Data are from a large hospital-based case-control study of persons treated for primary lung cancer at the Massachusetts General Hospital since 1992. Controls were drawn from friends and nonrelated family members. We genotyped 1,042 cases and 1,161 controls for GSTP1 using polymerase chain reaction-restriction fragment length polymorphism techniques. FINDINGS: The GSTP1 GG genotype approximately doubled the lung cancer risk associated with pack-years. This interaction was stronger among current smokers. At 26 pack-years (median among controls with a smoking history), the adjusted odds ratio for the association between pack-years and lung cancer risk was 13 (95% confidence interval = 6.5-25) among current smokers with the GSTP1 GG genotype compared with 6.1 (95% confidence interval = 4.9-7.5) among those with the GSTP1 AA genotype. CONCLUSIONS: GSTP1 GG increases the lung cancer risk associated with pack-years of smoking.