Genetic Polymorphisms in GSTM1, GSTP1, and GSTT1 and the Risk for Breast Cancer
Results from the Shanghai Breast Cancer Study and Meta-Analysis
- Kathleen M. Egan1,
- Qiuyin Cai1,
- Xiao-Ou Shu1,
- Fan Jin2,
- Tian-Li Zhu2,
- Qi Dai1,
- Yu-Tang Gao2 and
- Wei Zheng1
- 1Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, and 2 Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China
Abstract
Purpose: We studied the relation of breast cancer to common deletion mutations in GSTM1 and GSTT1 and the functional Ile105Val polymorphism in GSTP1 in a large, population-based case-control study conducted in China and performed a meta-analysis to summarize the literature.
Experimental Design: In the case-control study, a total of 1144 breast cancer cases and 1221 community controls were genotyped for GSTM1, GSTP1, and GSTT1 using PCR-based methods. Associations of genotypes and breast cancer were evaluated in logistic regression models. Meta-analysis odds ratios (ORs) were estimated using a fixed effects model.
Results: In the case-control study, associations were null for GSTM1 [age-adjusted OR 0.97, 95% confidence interval (CI): 0.82–1.14] and GSTT1 (OR 0.97, 95% CI: 0.83–1.15). A significant increase in risk was observed among homozygotes for the variant Ile105Val polymorphism (OR 1.92, 95% CI: 1.21–3.04). No combined effects of GSTM1, GSTP1, and GSTT1 genotypes or interactions with potential effect modifiers were detected. All results were similar in pre- and postmenopausal women and for early versus advanced stage breast cancer. The meta-analysis, based predominately on Caucasian women, supported null results for the homozygous deletion variant in GSTM1 (summary OR 1.05; combining 19 studies) and GSTT1 (summary OR 1.11; 15 studies). Meta-analysis results for the homozygous GSTP1 variant indicated no overall association (summary OR 1.04; 10 studies), although results varied significantly across studies (P = 0.009).
Conclusions: This large case-control study provides strong support for earlier studies showing no overall association of the GSTM1 and GSTT1 deletion polymorphisms with breast cancer risk. The GSTP1 variant may be relevant to breast cancer risk in Asian populations.
Footnotes
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Grant support: This research was supported by USPHS Grants RO1CA64277 and RO1CA90899 from the National Cancer Institute.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Requests for reprints: Dr. Kathleen M. Egan, Vanderbilt University Medical Center, Suite 6000, Medical Center East, Nashville, TN 37232-8300. Phone: (615) 936-1640; Fax: (615) 936-1269; E-mail: Kathleen.Egan{at}Vanderbilt.edu
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↵3 S. Boyapati, X. O. Shu, Y. T. Gao, Q. Dai, H. Yu, and J. R. Cheng. Correlation of blood sex steroid hormones with body size, body fat distribution, and other known risk factors for breast cancer in Chinese women, submitted for publication.
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↵4 Internet address: http://cgap.nci.nih.gov.
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- Accepted October 13, 1903.
- Received August 22, 1903.
- Revision received October 6, 1903.
