Association between glutathione S-transferase pi genetic polymorphisms andoral cancer risk

Polymorphisms in the gene encoding the glutathione S-transferase (GST) pi m etabolizing enzyme have previously been associated with susceptibility to v arious cancers, In this study, the importance of GSTP1 genotypes as determi nants of risk for oral cancer was assessed by examining the prevalence of G STP1 alleles in 157 incident oral cancer cases and 260 non-cancer control i ndividuals frequency-matched by race, sex, and age at diagnosis (+/- 5 year s). The GSTP1*A, GSTP1*B, GSTP1*C, and GSTP1*D alleles were elucidated by p olymerase chain reaction-restriction fragment length polymorphism analysis of polymorphisms present in codons 105 (isoleucine:valine) and 114 (alanine :valine) of the GSTP1 gene. Increased risk for oral cancer was observed in individuals who were homozygous for any combination of GSTP1 polymorphic al leles (i.e. *B, *C, and/or *D alleles; odds ratio = 2.4, 95% confidence int erval = 1.2-4.8). Similar risk was observed in both Caucasians (odds ratio = 2.6, 95% confidence interval = 1.1-6.2) and African-Americans (odds ratio = 2.3, 95% CI = 0.68-7.5). A greater risk was observed in individuals with the GSTP1 (Var/Var) genotype who were exposed to low levels of smoking (i. e less than or equal to 20 pack-years [py], odds ratio = 3.4, 35% confidenc e interval = 1.1-11) than among heavier smokers (i.e. > 20 pack-years [py], odds ratio = 1.4, 95% confidence interval = 0.48-4.0). These results sugge st that GSTP1 genotype may play a role in risk for oral cancer particularly among lighter smokers. Pharmacogenetics 9:497-504 (C) 1999 Lippincott Will iams & Wilkins.