Glutathione S-transferase gene polymorphisms and risk and survival of pancreatic cancer

BACKGROUND. Pancreatic cancer is a multifactorial disease with metastasis-prone and therapy-resistant nature. The authors hypothesized that genetic variants of glutathione S-transferase (GST) affect detoxification of carcinogens and anticancer agents in the human pancreas and, thus, the risk and survival of pancreatic cancer. METHODS. Genotypes of GSTM1, GSTT1, and GSTP1 were determined in 352 patients with pancreatic ductal adenocarcinoma and in a control group of 315 healthy, non-Hispanic whites (frequency-matched by age and sex). Survival analysis was performed in a subset of 290 patients. Epidemiological and clinical information was obtained. A multiple unconditional logistic regression model, a Cox proportional hazards model, and log-rank tests were used for statistical analysis. RESULTS. No significant main effects of any of 3 GST genes on the risk of pancreatic cancer were observed. Subgroup analysis showed that older individuals (aged ≥62 years) who carried the GSTP1*C (¹⁰⁵Val-¹¹⁴Val) containing genotype tended to have a reduced risk compared with younger individuals who carried the non-*C genotype (for sex and pack-years of smoking, the adjusted odd ratio was 0.54; 95% confidence interval [95% CI], 0.29-1.02). In a survival analysis of 138 patients who received 5-flurorouracil, patients who carried the GSTP1*C containing genotype had a significantly longer survival than patients who carried the non-*C genotype (multivariate hazard ratio, 0.45; 95% CI, 0.22-0.94). CONCLUSIONS. The GSTP1*C variant conferred a possible protective effect against pancreatic cancer in older individuals and a significant survival advantage in patients who received 5-florouracil. The current findings must be confirmed before further inferences can be made.