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. 2007 Mar 1;109(5):840-8.
doi: 10.1002/cncr.22468.

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

Li Jiao  1 , Melissa L Bondy, Manal M Hassan, David Z Chang, James L Abbruzzese, Douglas B Evans, Michael H Smolensky, Donghui Li
Affiliations

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

Li Jiao et al. Cancer. .

Abstract

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.

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Figures

FIGURE 1
FIGURE 1
The probability of survival is illustrated according to the presence of the glutathione S-transferase P1 (GSTP1) isoleucine (Ile)→valine (Val) exchange at codon 105 (Ile105Val) polymorphism in patients who received 5-fluorouracil (5-FU)-based chemotherapy/chemoradiation (A) and patients who received therapies other than 5-FU (B). P values were determined from log-rank tests.
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