Carcinogenesis Advance Access first published online on August 11, 2007
This version published online on August 29, 2007
Carcinogenesis, doi:10.1093/carcin/bgm141
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Interactions among GSTM1, GSTT1 and GSTP1 polymorphisms, cruciferous vegetable intake and breast cancer risk
1 Department of Nutrition, School of Public Health, University of North Carolina, Chapel Hill, NC
2 Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC
3 Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York, NY
4 Department of Epidemiology, Mailman School of Public Health
5 Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY
6 Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY
Address correspondence to: Susan E. Steck, Ph.D., MPH, Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, 2221 Devine Street, Room 231, Columbia, SC 29208, Fax: 803-734-5505 Email: ssteck{at}sc.edu
Isothiocyanates are anticarcinogenic phytochemicals found in cruciferous vegetables that both induce and are substrates for the gluthatione S-transferases (GSTs). The GSTs are phase II metabolizing enzymes involved in metabolism of various bioactive compounds. Functional polymorphisms in GST genes have been identified and may interact with cruciferous vegetable intake to affect cancer risk. We examined this hypothesis using data from the Long Island Breast Cancer Study Project, a population-based case-control study conducted in Long Island, NY from 1996-1997. Cruciferous vegetable intake in the previous year was assessed via modified Block food frequency questionnaire. DNA was extracted from blood samples (n=1052 cases and n=1098 controls) and genotyped for GSTM1 deletion, GSTT1 deletion and GSTP1 Ile105Val using multiplex PCR and Taqman assays. Unconditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). We found an 86% increase in the OR for breast cancer among carriers of the GSTM1 null, GSTT1 null and GSTP 105Ile/Ile genotypes (OR=1.86, 95% CI=1.12, 3.08) and a 36% decrease in the OR among carriers of GSTM1 present, GSTT1 null and GSTP1 105Ile/Val+Val/Val genotypes (OR=0.64, 95% CI=0.42, 0.97) compared to GSTM1 present, GSTT1 present and GSTP1 105Ile/Ile carriers. We found no joint effects among GST polymorphisms and cruciferous vegetable intake and breast cancer risk. In conclusion, we found associations between specific combinations of three GST gene polymorphisms and breast cancer risk but these did not modify the association between cruciferous vegetable intake and breast cancer. Additional studies are needed to confirm the associations observed.
Key Words: breast cancer • GST • cruciferous vegetable • isothiocyanate
Received February 22, 2007; revised June 15, 2007; accepted June 18, 2007.