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University of Toronto and Sunnybrook-Women’s College Health Sciences Centre, Toronto, Ontario M5G 1N8, Canada [A. L., W. W. Z., S. A. N.]; Department of Surgery, College of Medicine and Philippine General Hospital, University of the Philippines, Manila, Philippines [M. L. D. L. M.]; Department of Surgery, Davao Regional Hospital, Tagum City, Philippines [A. T.]; and Women’s Cancer Research Institute, Cedars-Sinai Medical Center, Los Angeles, California [A. L.]
Up to one-third of women with breast cancer have a family history of breast cancer, and 
5% of cases are attributed to mutations in high-risk breast cancer susceptibility genes, such as BRCA1 and BRCA2. It is believed that genes of lower penetrance, but of greater prevalence, may also modulate a woman’s risk of breast cancer. We studied the association of breast cancer and the trinucleotide repeat polymorphism (CAGn) in exon 1 of the androgen receptor gene (AR) in 299 cases of breast cancer and in 229 hospital-based controls from the Philippines. Women for whom the mean length of the CAG repeat allele was 
25 units had approximately one-half of the risk of breast cancer compared with women with a mean repeat length of 
26 [odds ratio (OR), 0.47; 95% confidence interval (CI), 0.28–0.8). The association with breast cancer risk was particularly strong among older women (50 years; OR, 0.2; 95% CI, 0.04–0.94). The association was also observed for the longer of the two AR alleles; there was a 5% increase in breast cancer risk for each unit increase in CAG repeat number. These findings support the theory that short trinucleotide repeat genotypes of the AR gene protect against breast cancer.
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