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Genetic Variation in Angiotensin I-Converting Enzyme (ACE) and Breast Cancer Risk

The Multiethnic Cohort¹

Departments of Preventive Medicine [C. A. H., S. O. H., P. B., B. E. H.] and Emergency Medicine [S. O. H.], University of Southern California, Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, California 90089, and Cancer Etiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii 96813 [L. N. K.]

The A-240T and I/D polymorphisms in the angiotensin I-converting enzyme (ACE) gene are markers of circulating ACE levels and have been associated with numerous cardiovascular disease outcomes. More recently, the low-activity A and I alleles at these polymorphic sites have been inversely related with breast cancer risk. We assessed the relationship between the A-240T and I/D ACE variants and breast cancer risk in a case-control analysis (n = 1263 cases with invasive breast cancer and 2269 controls) among African-American, Japanese, Latina, and white women in the Multiethnic Cohort Study. Odds ratios and 95% confidence intervals are presented adjusted for established breast cancer risk factors. Among all women combined, we observed no significant association between the A-240T polymorphism and breast cancer risk. For the I/D polymorphism, contrary to expectation, women with the I/I genotype had a marginally significant increase in breast cancer risk (versus DD genotype: odds ratio, 1.30; 95% confidence interval, 1.05–1.61), although associations were not entirely consistent across ethnic groups. These data do not support the hypothesis that women with lower ACE levels, as predicted by the low-activity A and I ACE alleles, are at reduced risk of breast cancer. Overall, these results suggest that the A-240T and I/D ACE polymorphisms are not likely to be strong predictors of breast cancer risk.

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