Glutathione Gene Polymorphism Protects Against Pancreatic Cancer in Elderly People

Melissa Bondy, Ph.D.
The University of Texas M.D. Anderson Cancer Center
P30ES007784

Each year in the United States, slightly less than 34,000 people are diagnosed with pancreatic cancer and slightly more than 32,000 of them will die within five years of diagnosis with about half dying within 6 months. Pancreatic cancer is very difficult to treat. The only known risk factor for the malignancy is smoking and very little is known about how genetic and environmental factors interact to lead to the disease.

Melissa Bondy and her colleagues at the University of Texas M.D. Anderson Cancer Center hypothesized that genetic variations in the detoxifying enzyme glutathione S-transferase (GST) affect the detoxification of carcinogenic agents and chemotherapeutic agents in the pancreas, thus affecting the risk and survival of pancreatic cancer. They studied 352 pancreatic cancer patients and matched them to 315 healthy control subjects.

The study results show that older individuals with the GST polymorphism known as GSTP1*C had a reduced risk of pancreatic cancer than younger individuals with the“non­*C” genotype, and in 5­flurouracil treated patients, those with the GSTP1*C lived significantly longer, about six months. This study is believed to be the first to suggest a protective affect of GSTP1 polymorphisms in pancreatic cancer.

The authors conclude that genetic polymorphisms of GSTP1 could be one of the possible mechanisms that modify the risk of pancreatic cancer in older people and possibly affect the survival rate. They caution that risk and survival are the result of the interplay of multiple genes in different pathways. They suggest that additional studies are needed to confirm or refute these findings and to further the understanding of the roles of genetic differences and regulatory mechanisms of glutathione and other factors in pancreatic carcinogenesis and treatment management.

Citation: Jiao L, Bondy ML, Hassan MM, Chang DZ, Abbruzzese JL, Evans DB, Smolensky MH, Li D. Glutathione S-transferase gene polymorphisms and risk and survival of pancreatic cancer. Cancer. 2007 Mar 1;109(5):840-8.