Carcinogenesis Advance Access originally published online on April 19, 2006
Carcinogenesis 2006 27(9):1876-1882; doi:10.1093/carcin/bgl038
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Effects of glutathione S-transferase A1 (GSTA1) genotype and potential modifiers on breast cancer risk
1 Department of Epidemiology Buffalo, NY 14263, USA
2 Department of Chemoprevention Roswell Park Cancer Institute Buffalo, NY 14263, USA
3 Division of Nutritional Sciences, Cornell University Ithaca, NY 14853, USA
4 Department of Epidemiology, School of Public Health, University of North Carolina Chapel Hill, NC 27599, USA
5 Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University New York, NY 10032, USA
6 Department of Epidemiology, Mailman School of Public Health, Columbia University New York, NY 10032, USA
7 Department of Medicine, College of Physicians and Surgeons, Columbia University New York, NY 10032, USA
8 Department of Community and Preventive Medicine, Mount Sinai School of Medicine New York, NY 10029, USA
9 Global Epidemiology, Safety and Risk Management, Pfizer Inc. New York, NY, USA
*To whom correspondence should be addressed. Tel: +1 301/451 9581; Fax: 301/496 6829; Email: ahnj{at}mail.nih.gov
Glutathione S-transferases (GSTs) are phase II enzymes that are involved in the detoxification of a wide range of carcinogens. The novel GSTA1*A and GSTA1*B genetic polymorphism results in differential expression, with lower transcriptional activation of GSTA1*B (variant) than that of GSTA1*A (common) allele. Considering that cruciferous vegetables induce GSTs, which metabolize tobacco smoke carcinogens, we hypothesized that the variant GSTA1*B genotype may predispose women to breast cancer, particularly among low cruciferous vegetable consumers and among smokers. Thus, we evaluated potential relationships between GSTA1 polymorphisms and breast cancer risk, in relation to vegetable consumption and smoking status in the Long Island Breast Cancer Study Project (1996–1997), a population-based case–control study. Genotyping (1036 cases and 1089 controls) was performed, and putative breast cancer risk factors and usual dietary intakes were assessed. Having GSTA1*A/*B or *B/*B genotypes was not associated with increased breast cancer risk, compared to having the common *A/*A genotype. However, among women in the lowest two tertiles of cruciferous vegetable consumption, *B/*B genotypes were associated with increased risk (OR (95% CI) = 1.73 (1.10–2.72) for 0–1 servings/week), compared to women with *A/*A genotypes. Among women with *B/*B genotypes, a significant inverse trend between cruciferous vegetable consumption and breast cancer risk was observed (P for trend = 0.05), and higher consumption (4+ servings/week) ameliorated the increased risk associated with the genotype. Current smokers with *B/*B genotypes had a 1.89-fold increase in risk (OR (95% CI) = 1.89 (1.09–3.25)), compared with never smokers with *A/*A genotypes. These data indicate that GSTA1 genotypes related to reduced GSTA1 expression are associated with increased breast cancer primarily among women with lower consumption of cruciferous vegetables and among current smokers.
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