Journal
CANCER
Volume 109, Issue 5, Pages 840-848Publisher
WILEY
DOI: 10.1002/cncr.22468
Keywords
glutathione S-transferase M1 (GSTM; GSTT1; GSTP1; polymorphism; haplotype; risk; survival; pancreatic cancer
Categories
Funding
- NCI NIH HHS [CA84581, R01 CA098380, R03 CA084581, P30 CA016672, CA16672, CA98380] Funding Source: Medline
- NIEHS NIH HHS [P30 ES07784, P30 ES007784] Funding Source: Medline
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BACKGROUND. Pancreatic cancer is a multifactorial disease with metastasis -prone and therapy- resistant nature. The authors hypothesized that genetic variants of glutathione S-transterase (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 adenocarcinorna 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 ((105)Val-(114)Val) 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 GSTPI*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.
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