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Androgen Receptor (CAG)_n and (GGC)_n Polymorphisms and Breast Cancer Risk in a Population-Based Case-Control Study of Young Women¹

Divisions of Clinical Research and Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024 [N. M. S., E. A. O.]; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024 [K. E. M., J. R. D., D. R. D.]; and School of Public, Health and Community Medicine, Department of Epidemiology, University of Washington, Seattle, Washington 98195 [K. E. M., J. R. D.]

The androgen receptor (AR) is involved in the regulation of hormone-responsive genes and, as such, variation within the gene is hypothesized to play a role in breast cancer susceptibility. We therefore assessed the relationship between AR repeat variation and breast cancer in young women from the general population. Women diagnosed with breast cancer before age 45 years and age-matched controls, all participants in a population-based case-control study of breast cancer, were assessed for length variation in the (CAG)_n and (GGC)_n AR repeats within the AR gene. Results were generated from 524 cases and 461 controls. As per previous studies, (CAG)_n repeat lengths of <22 were classified as short (S), and those of 22 were classified as long (L). For (GGC)_n repeats, those < 17 were classified as short, and those 17 were classified as long. Women with a cumulative (CAG)_n repeat size of 43 showed a modest increase in risk for breast cancer [odds ratio (OR), 1.3; 95% confidence interval (CI), 1.0–1.7]. Women with a (GGC)_n long (L) allele and those with a 33 cumulative repeat size had a decreased risk of breast cancer (OR, 0.7; 95% CI, 0.5–0.9). Among women homozygous for the (CAG)_n short (S) allele and those with any (GGC)_n L allele, an increased risk of breast cancer in relation to ever use of oral contraceptives [OCs; OR = 1.9 (95% CI, 1.0–3.6) and OR = 1.7 (95% CI, 0.9–3.5), respectively] was observed. An increased risk for OC use, however, was not observed among women with the CAG L or GGC S allele. This study, one of the first to examine both (CAG)_n and (GGC)_n in a population-based study for its relation to breast cancer risk, suggests a reduced risk in young women with (GGC)_n repeat lengths of 17. In addition, these data suggest that AR repeat length may be partly responsible for the increased risk for early-onset breast cancer in women who use OCs, although these findings need replication in other populations.

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