Glutathione S-transferase polymorphisms and survival in African-American and white colorectal cancer patients.

ABSTRACT

BACKGROUND: Glutathione S-transferase (GST) enzymes are involved in electrophile detoxification. The authors investigated the association between GST genotype and survival in a racially diverse, population-based cohort of colorectal cancer (CRC) patients followed for a median of 9.6 years. METHODS: Interviews were conducted with 315 African-American and White CRC patients in Connecticut, 1987-1991. Tumor tissue (n=197) was later retrieved from hospital of diagnosis and assayed using multiplex PCR (GSTM1 and GSTT1) and PCR and RFLP analysis (GSTP1). Cox proportional hazards models provided adjusted hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Individuals with Ile/Val or Val/Val GSTP1 genotypes had a decreased risk of death (multivariate adjusted HR=0.72, 95% CI 0.48, 1.09) relative to those with wild type (Ile/Ile). Among those who received chemotherapy, this benefit was more pronounced (HR=0.35, 95% CI 0.16, 0.79); the interaction of reduced function GSTP1 genotype and chemotherapy was significant (P=0.05). GSTM1 and GSTT1 genotype were not associated with survival. GSTM1, GSTT1, and GSTP1 genotype did not vary by race and did not contribute significantly to the survival disadvantage observed in African-Americans. CONCLUSIONS: In summary, GSTP1 genotype may play a role in CRC survival in African-Americans and Whites, particularly among those who receive chemotherapy.