Glutathione S-Transferase Polymorphism Increases Risk of Second Primary Malignancy

Guojun Li, M.D., Ph.D.,
University of Texas M.D. Anderson Cancer Center
NIEHS Grant R01ES011740

A large prospective cohort study suggests that people with certain polymorphisms of the glutathione S-transferase (GST) genes are more likely to develop a second primary malignancy after first developing squamous cell carcinoma of the head and neck. The study reports a 1.7-fold increase for people with the GSTP1 Ile105Val polymorphism and an even greater risk for multiple GST risk genotypes.

Most squamous cell carcinomas of the head and neck area are attributable to tobacco and alcohol. Cigarette smokers are at about a 10-fold higher risk of developing the cancer than people who have never smoked. Alcohol consumption is known to contribute to the risk, but most smokers and drinkers never develop squamous cell carcinoma suggesting that genetic susceptibility plays a significant role in the development of the cancer. Traditional cancer therapies cure many squamous cell carcinomas, but a significant proportion of patients go on to develop a second primary malignancy.

GSTs are known to detoxify many carcinogens in tobacco smoke. The research team hypothesized that variations in the genes coding for GSTs might alter a person’s risk for developing a second malignancy. Identifying markers of risk for later malignancies among cancer survivors could greatly enhance secondary cancer prevention efforts. By screening patients for these genetic variations, physicians could identify those patients more likely to develop additional cancers and target them for more stringent intervention regimens and closer follow-up to prevent additional cancers or identify them at earlier stages.

Citation: Zafereo ME, Sturgis EM, Aleem S, Chaung K, Wei Q, Li G. Glutathione S-transferase polymorphisms and risk of second primary malignancy after index squamous cell carcinoma of the head and neck. Cancer Prev Res (Phila Pa). 2009 May;2(5):432-9.