Polymorphic expression of the glutathione S-transferase P1 gene and its susceptibility to Barrett's esophagus and esophageal carcinoma

Factors determining individual susceptibility to esophageal cancer or prema lignant Barrett's epithelium are still largely unclear. An imbalance betwee n phase I drug metabolism [e.g., cytochrome P450 (CYP)] and phase II detoxi fication [e.g., glutathione S-transferase (GST)] may contribute to the deve lopment of these diseases. polymorphic variants in the CYPIA1 gene were des cribed leading to increased levels of bioactive compounds, whereas polymorp hisms in GST genes often resulted in impaired detoxification. We studied th e frequencies of polymorphic variants in CYPIA1, GSTP1, GSTT1, and GSTM1 ge nes in 98 patients with Barrett's epithelium and 34 patients with esophagea l cancer, The results were compared with those obtained from 247 healthy bl ood donors. DNA was extracted, and PCR-RFLP methods were used to detect gen etic polymorphisms. chi(2) analysis, Spearman rank correlation, and Wilcoxo n rank sum tests were used for statistical evaluation, Polymorphisms in CYP IA1, GSTM1, and GSTT1 occurred at an equal frequency in patients and contro ls, Occurrence of the polymorphic GSTP1b variant in the GSTP1 gene resulted in a significantly lower GST enzyme activity (P < 0.05), and GSTP1b was fo und significantly more often in patients with Barrett's epithelium (70%; P < 0.001) and patients with esophageal adenocarcinoma (76%; P = 0.005), as c ompared to healthy blood donors (41%). In conclusion, presence of the GSTP1 b allele leads to lower GST enzyme activity levels and, consequently, impai red detoxification, This most important esophageal GST isoform may, therefo re, contribute to the development of Barrett's epithelium and adenocarcinom a.