Carcinogenesis Advance Access published online on April 19, 2006
Carcinogenesis, doi:10.1093/carcin/bgl038
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Epidemiology, Roswell Park Cancer Institute, Buffalo, NY 14263; Division of Nutritional Sciences, Cornell University, Ithaca, NY, 14853
* To whom correspondence should be addressed. 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 (1,036 cases and 1,089 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.
Received October 4, 2005
Revised March 29, 2006
Accepted March 31, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Effects of glutathione S-transferase A1 (GSTA1) genotype and potential modifiers on breast cancer risk
Jiyoung Ahn 1 *,
Marilie D. Gammon 2,
Regina M. Santella 3,
Mia M. Gaudet 2,
Julie A. Britton 4,
Susan L. Teitelbaum 4,
Mary Beth Terry 5,
Alfred I. Neugut 6,
Sybil M. Eng 7,
Yuesheng Zhang 8,
Cutberto Garza 9,
and
Christine B. Ambrosone 10
2 Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, 27599-7435
3 Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, 10032
4 Department of Community, Mount Sinai School of Medicine, New York, NY, 10029; Department of Preventive Medicine, Mount Sinai School of Medicine, New York, NY, 10029
5 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032
6 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032; Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032
7 Global Epidemiology, Safety and Risk Management, Pfizer, Inc., New York, NY
8 Department of Chemoprevention, Roswell Park Cancer Institute, Buffalo, NY 14263
9 Division of Nutritional Sciences, Cornell University, Ithaca, NY, 14853
10 Department of Epidemiology, Roswell Park Cancer Institute, Buffalo, NY 14263
Jiyoung Ahn, E-mail: ahnj{at}mail.nih.gov
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S.-A. Lee, J. H Fowke, W. Lu, C. Ye, Y. Zheng, Q. Cai, K. Gu, Y.-T. Gao, X.-o. Shu, and W. Zheng Cruciferous vegetables, the GSTP1 Ile105Val genetic polymorphism, and breast cancer risk Am. J. Clinical Nutrition, March 1, 2008; 87(3): 753 - 760. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Steck, M. D. Gammon, J. R. Hebert, D. E. Wall, and S. H. Zeisel GSTM1, GSTT1, GSTP1, and GSTA1 Polymorphisms and Urinary Isothiocyanate Metabolites following Broccoli Consumption in Humans J. Nutr., April 1, 2007; 137(4): 904 - 909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Was, T. Cichon, R. Smolarczyk, D. Rudnicka, M. Stopa, C. Chevalier, J. J. Leger, B. Lackowska, A. Grochot, K. Bojkowska, et al. Overexpression of Heme Oxygenase-1 in Murine Melanoma: Increased Proliferation and Viability of Tumor Cells, Decreased Survival of Mice Am. J. Pathol., December 1, 2006; 169(6): 2181 - 2198. [Abstract] [Full Text] [PDF]
|
|