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

Journal Article (Journal Article)

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 >or=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 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.

Full Text

Duke Authors

Cited Authors

  • Jiao, L; Bondy, ML; Hassan, MM; Chang, DZ; Abbruzzese, JL; Evans, DB; Smolensky, MH; Li, D

Published Date

  • March 1, 2007

Published In

Volume / Issue

  • 109 / 5

Start / End Page

  • 840 - 848

PubMed ID

  • 17265526

Pubmed Central ID

  • PMC1892189

International Standard Serial Number (ISSN)

  • 0008-543X

Digital Object Identifier (DOI)

  • 10.1002/cncr.22468


  • eng

Conference Location

  • United States