Abstract 5604: Microsatellites in the estrogen (ESR1, ESR2) and androgen receptor (AR) genes and risk of breast cancer in women of African ancestry

Background: Breast cancer is a major global problem, with approximately 1 million cases diagnosed each year. A joint effect of genetic as well as endogenous and exogenous factors contributes to an increased risk for breast cancer development. Hormone receptor genes may be crucial predisposing factors, and genetic variations such as microsatellites/short tandem repeats (STRs) in the estrogen and androgen receptor genes (ESR1, ESR2 and AR) have been suggested to play a role. Historically, breast cancer studies were understudied in women of African ancestry who have a remarkable higher proportion of poorly differentiated tumors that lack estrogen receptor (ER) expression and present in advanced stages. Methods: We studied 258 African-American (AA) women with breast cancer (age of onset = 44.1 ± 10.0 yr [mean ± SD]) and 259 hospital-based controls (age = 46.8 ± 10.9 yr), as well as 349 Nigerian (NG) female breast cancer patients (age of onset = 47.5 ± 11.7 yr) and 293 community controls (age = 41.5 ± 14.1 yr). Three microsatellites ESR1_TA, ESR2_CA and AR_CAG in the ESR1, ESR2 and AR gene, respectively, were genotyped. The lengths of repeats were then analyzed as continuous and dichotomous variables. Associations between the three STRs and breast cancer were assessed using Mann-Whitney test and logistic regression method. Results: Overall, the allele distributions of each individual microsatellite between AA and NG are similar. Analyses of continuous variables showed: 1) no association in neither AA nor NG at ESR1_TA; 2) AA cases have shorter repeats in the large allele of ESR2_CA than AA controls (Mann-Whitney P = 0.036; logistic regression P = 0.041, OR per allele = 0.907 (95% CI 0.827-0.996), whereas NG patients have longer repeats in the small allele than NG controls (Mann-Whitney P = 0.002; logistic regression P = 0.040, OR = 1.056 (95% CI 1.002-1.113); and 3) AA cases appear to carry longer repeats in the small allele of AR_CAG than AA controls (Mann-Whitney P = 0.038; logistic regression P = 0.027, OR = 1.076 (95% CI 1.008-1.149). When allele sizes were categorized as dichotomous variables, the mean repeat numbers in controls were selected to be cutoffs. We found that women with two large alleles of ESR2_CA had increased risk of breast cancer (OR = 1.38, 95% CI 1.10-1.74; P = 0.006). Conclusion: This is the first study to investigate the STRs in hormonal receptor genes and the risk of breast cancer in a Nigerian population. Among women of African ancestry, common microsatellites of the ESR2 and AR genes are associated with risk of breast cancer, at least partially. They could be useful genetic markers to estimate disease risk, although these findings require further replication in larger cohort of women of African ancestry. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5604. doi:10.1158/1538-7445.AM2011-5604