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Epidemiology and Prevention |
Departments of Epidemiology [C. A. H., S. E. H., D. S., G. A. C., W. C. W., D. J. H.], Biostatistics [D. S.], and Nutrition [W. C. W., D. J. H.], and the Harvard Center for Cancer Prevention [C. A. H., G. A. C., W. C. W., D. J. H.], Harvard School of Public Health, Boston, Massachusetts 02115; Channing Laboratory [S. E. H., G. A. C., W. C. W., D. J. H.] and Department of Medicine [M. B.], Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115; The Lank Center for Genitourinary Oncology [P. W. K.] and Department of Adult Oncology [M. B., P. W. K.], Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and Department of Preventive Medicine [C. A. H.], USC/Norris Comprehensive Cancer Center, Los Angeles, California 90089
Shorter alleles of a polymorphic [CAG]n repeat in exon 1 of the androgen receptor (AR) have been associated with increased risk of prostate cancer and decreased risk of breast cancer. We prospectively assessed the association between the [CAG]n repeat polymorphism in the androgen receptor and breast cancer risk among Caucasian women in a case-control study nested within the Nurses’ Health Study cohort (cases, n = 727; controls, n = 969). In addition, we assessed whether androgen receptor genotype influences endogenous steroid hormone levels in women and whether the associations between androgen receptor alleles and breast cancer risk differed according to established breast cancer risk factors. Women with one or more long AR [CAG]n repeat alleles (
22 repeats) were not at increased risk of breast cancer [odds ratio (OR), 1.06; 95% confidence interval (CI), 0.83–1.35]. Significant associations were not observed between AR genotypes comprised of two short alleles ([CAG]n 
20 versus both alleles 22: OR, 0.92; 95% CI, 0.62–1.36) or two long alleles ([CAG]n 25 versus both alleles 22: OR, 1.42; 95% CI, 0.81–2.50) and breast cancer risk. We also observed no strong overall association between average repeat length and breast cancer risk (OR, 1.04 per CAG repeat; 95% CI, 0.99–1.10) or between average repeat length and plasma hormone levels. We also examined the cross-classification of AR genotype and first-degree family history of breast cancer. Compared with women with both alleles <22 and no family history, we observed a significant positive association limited to women with both a first-degree family history of breast cancer and longer alleles (one or two [CAG]n alleles 22; OR, 1.70; 95% CI, 1.20–2.40; P for interaction = 0.04). In summary, we observed no overall relation of AR genotype with breast cancer risk among mostly postmenopausal Caucasian women. However, these data suggest that longer AR [CAG]n repeat alleles may increase breast cancer risk among women with a first-degree family history of breast cancer.
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