Androgen Receptor (AR) and Estrogen Receptor alpha (ER) Variants Have Minimal Impact upon Cancer Susceptibility in BRCA1 Mutation Carriers. S. Harbord¹, C.J. Brown¹, D. Horsman^1,2, S. Young², W.P. Robinson¹. 1) Depts. of Medical Genetics and Pathology, UBC; 2) BC Cancer Agency; Vancouver BC Canada.
   A mutation in the BRCA1 gene dramatically increases a womans chance of developing breast and/or ovarian cancer, however, penetrance is incomplete. Epidemiological data implicates hormones in both the presence and the severity of breast and ovarian cancers, and hormone receptor activity has been linked to BRCA1 protein activity. Polymorphisms in hormone receptors may act as genetic modifiers and influence risk of breast and/or ovarian cancer in BRCA1 mutation carriers. Androgen Receptor (AR) and Estrogen Receptor alpha (ER) contain polymorphisms that have been associated with breast cancer, though results have been inconsistent. Here we have studied AR CAG repeat length, ER TA repeat length and two ER SNP polymorphisms at -397 and -351 in 42 affected BRCA1 mutation carriers, 15 unaffected BRCA1 mutation carriers, 24 BRCA2 mutation carriers, 24 familial controls and 152 population controls. Repeat length was determined using a conventional PCR-based assay, while ER SNP polymorphisms were analyzed by allelic discrimination with Real Time PCR. Despite previous reports, no patient group was significantly different from controls for any hormone receptor polymorphism considered. Neither affected BRCA1 mutation carriers nor affected non-BRCA1 mutation carriers had an increase in long AR alleles when compared to pooled familial and population controls (BRCA1: 7/42, non-BRCA1: 4/33, controls: 30/186). Affected BRCA1 mutation carriers had a non-significant trend towards a decrease in long AR alleles when compared to combined controls (BRCA1: 12/42, controls: 33/186). Long ER TA repeats were also not increased in affected BRCA1 mutation carriers (29/42) or affected non-BRCA1 mutation carriers (20/33) compared to combined controls (80/128). In addition, no ER SNP polymorphism is overabundant in either affected BRCA1 mutation carriers or affected non-BRCA1 mutation carriers compared to controls. Though sample size is small, it seems that androgen receptor and estrogen receptor a variants do not largely affect breast and/or ovarian cancer risk in BRCA1 mutation carriers.