Androgen Receptor Exon 1 CAG Repeat Length and Breast Cancer in Women Before Age Forty Years

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Abstract
BACKGROUND: We conducted a population-based, case-control-family study to determine whether androgen receptor (AR) exon 1 polymorphic CAG repeat length (CAG n ) was a risk factor for early-onset breast cancer in the Australian population. METHODS: Case subjects under 40 years of age at diagnosis of a first primary breast cancer and age-matched control subjects were interviewed to assess family history and other risk factors. AR CAG n length was determined for 368 case subjects and 284 control subjects. Distributions in the two groups were compared by linear and logistic regression, allowing adjustment for measured risk factors. All statistical tests were two-tailed. RESULTS: When analyzed as either a continuous or a dichotomous variable, there was no association between CAG n length and breast cancer risk, before or after adjustment for risk factors. Mean (95% confidence interval [CI]) CAG n lengths were 22.0 (21.8-22.2) for case subjects and 22.0 (21.7-22.3) for control subjects ( P = .9). The frequency (95% CI) of alleles with 22 or more CAG n repeats was 0.531 (0.494-0.568) for case subjects and 0.507 (0.465-0.549) for control subjects ( P = .4). After adjustment, the average effect on log OR (odds ratio) per allele was 0.16 (95% CI = −0.03 to 0.40; P = .2), and the effect of any allele was equivalent to an OR of 1.40 (95% CI = 0.94-2.09; P = .1). Stratification by family history also failed to reveal any association. Similar results were obtained when alleles were defined by other cutoff points. CONCLUSION: We found no evidence for an association between AR exon 1 CAG n length and breast cancer risk in women under the age of 40, despite having 80% power to detect modest effects.