Human glutathione S-transferase P1 polymorphism and susceptibility to smoking related epithelial cancer; oral, lung, gastric, colorectal and urothelial cancer

The A/G polymorphism at nucleotide 313 in the glutathione S-transferase P1- 1 (GSTP1) gene was examined in patients with different types of smoking-rel ated cancers (oral, lung, gastric, colorectal and urothelial cancers) and h ealthy control individuals. This polymorphism results in an amino acid subs titution from isoleucine to valine at residue 105, which reduces catalytic activity of the enzyme. In control individuals, 23.8% of individuals had GS TP1 AG or GG genotype. This rose to 37.3% [n = 83, odds ratio = 1.93 (1.05- 3.58), P = 0.035] in oral cancer patients. No increase in the frequency of the GSTP1 AG or GG genotype was obtained in lung, gastric, colorectal or ur othelial cancers in this Japanese population. After grouping by smoking sta tus, no consistent difference was observed between smoking patients and cor responding control individuals for the frequency of the GSTP1 A/G polymorph ism for any cancer. However, a moderate risk (odds ratio = 2.78; 95% confid ence interval 1.06-7.51) was associated with this polymorphism in the non-s moking group of oral cancer patients. The results suggest the GSTP1 polymor phism at nucleotide 313 may be associated with susceptibility to oral squam ous cell carcinoma in the Japanese population. Pharmacogenetics 9:165-169 ( C) 1999 Lippincott Williams & Wilkins.