Carcinogenesis Advance Access published online on July 15, 2004
Carcinogenesis, doi:10.1093/carcin/bgh230
© 2004 by Oxford University Press
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1 USC/Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, Los Angeles, California 90033-0800
* To whom correspondence should be addressed. E-mail: mgago{at}usc.edu.
We have previously found marine n-3 fatty acids to be inversely related to postmenopausal breast cancer in Chinese women from Singapore (1). Postmenopausal women with high [quartiles 2-4 (Q2-Q4)] versus low [quartile 1 (Q1)] intake exhibited a statistically significant reduction in risk of breast cancer after adjustment for potential confounders (relative risk (RR) = 0.66, 95% confidence interval (CI) = 0.50, 0.87). Experimental studies have demonstrated a direct role for the peroxidation products of marine n-3 fatty acids in breast cancer protection. There is suggestion that the glutathione S-transferases (GSTs) may be major catalysts in the elimination of these beneficial byproducts. Therefore, we hypothesized that individuals possessing the low activity genotypes of GSTM1, GSTT1 and/or GSTP1 (i.e., GSTM1-null, GSTT1-null and GSTP1 AB/BB genotypes, respectively) may exhibit a stronger marine n-3 fatty acids-breast cancer association than their high activity counterparts. The Singapore Chinese Health Study is a prospective investigation involving 35,298 middle-aged and older women, who were enrolled between April 1993 and December 1998. In this case-control analysis nested within the Singapore Chinese Health Study, we compared 258 incident breast cancer cases with 670 cohort controls. Overall, breast cancer risk was unrelated to GSTM1 and GSTP1 genotypes. However, GSTT1-null genotype was associated with a 30% reduced risk of breast cancer (OR = 0.71, 95% CI = 0.52, 0.96). Among women with high activity GST genotypes (i.e., GSTM1-positive, GSTT1-positive, GSTP1-AA), no marine n-3 fatty acid-breast cancer relationships were observed in either premenopausal or postmenopausal women at baseline. However, postmenopausal women possessing the combined GSTM1-null and GSTP1-AB/BB genotypes showed a statistically significant reduction in risk after adjustment for potential confounders (Q2-Q4 versus Q1, OR = 0.36, 95% CI = 0.14, 0.94). A similar relationship was observed among women with the combined GSTT1-null and GSTP1-AB/BB genotypes (OR = 0.26, 95% CI = 0.08, 0.78).
Revised May 18, 2004
Accepted July 6, 2004
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Marine n-3 fatty acid intake, glutathione S-transferase polymorphisms and breast cancer risk in postmenopausal chinese women in Singapore
2 Department of Community, Occupational and Family Medicine, National University of Singapore, 16 Medical Drive, Singapore 117597
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