Glutathione S-transferase Polymorphisms, Cruciferous Vegetable Intake, and Kidney Cancer Risk in Central and Eastern Europe

Abstract

ISEE-799 Objective: High consumption of cruciferous vegetables has been associated with reduced kidney cancer risk in several studies. Isothiocyanates, thought to be responsible for the chemopreventive properties of this food group, are conjugated to glutathione by glutathione S-transferases (GSTs) before urinary excretion. Modification of this association by common functional GST polymorphisms has never been assessed. Materials and Methods: We investigated cruciferous vegetable intake in 1097 cases and 1555 controls enrolled in a multicentric case-control study from the Czech Republic, Poland, Romania, and Russia. To determine whether genetic variation could modify associations between kidney cancer risk and cruciferous vegetable intake, we genotyped cases and controls for selected functional or nonsynonymous polymorphisms, including the GSTM1 deletion, GSTM3-three base pair deletion (IVS6 +22-AGG), and V224I G > A substitution, GSTT1 deletion, and the GSTP1 I105V A > G substitution. Genotyping assays were conducted at the Core Genotyping Facility at the National Cancer Institute as described online at http://snp500cancer.nci.nih.gov/home.cfm. Results: The odds ratio (OR) for low (less than once per month) versus high (at least once per week) intake of cruciferous vegetables was 1.29 [95% confidence interval (CI): 1.02–1.62; P-trend = 0.03]. When low intake of cruciferous vegetables (<1/month) was stratified by GST genotype, higher kidney cancer risks were observed among individuals with the GSTT1 null (OR = 1.86; 95% CI:1.07–3.23; P-interaction = 0.05) or with both GSTM1/T1 null genotypes (OR = 2.49; 95% CI:1.08–5.77; P-interaction = 0.05). Conclusions: These data provide additional evidence for the role of cruciferous vegetables in cancer prevention and add to the growing weight of evidence supporting a role for common, functional genetic polymorphisms in modifying cancer risk.