Abstract A107: Variation in the prolactin and prolactin receptor genes and familial breast cancer

Abstract

Abstract Background: Breast cancer aggregates within some families, accounting for about 25% of incident cases. Known genetic variants, such as BRCA1/BRCA2 mutations, account for less than 10% of these familial breast cancer cases, thus, research into additional risk or protective genetic factors for familial breast cancer may provide valuable information for risk stratification. Serum levels of prolactin have been associated with sporadic breast cancer risk in previous studies. We sought to test the hypothesis that variation in the genes coding for prolactin (PRL) and the prolactin receptor (PRLR) would be associated with increased or decreased risk of familial breast cancer. Methods: We designed a case-control study of probands recruited between 1998 and 2009 by the UCLA Family Cancer Registry; a population enriched with women having a strong family history of breast cancer and BRCA1/BRCA2 mutation carriers. Genotyping of tagSNPs in PRL (n=11) and PRLR (n=28) was performed in 351 unrelated women who developed breast cancer and 290 unaffected controls with similar family histories to the cases. Multivariate logistic regression models controlling for age, Ashkenazi Jewish heritage, education, and number of affected relatives were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between SNPs and familial breast cancer. Genotype specific ORs as well as per-allele (additive model) ORs were calculated. Results: Familial breast cancer risk was inversely associated with carriership of the minor alleles for three PRLR SNPs in the additive models, rs9292573 (OR=0.7, 95% CI=0.5-0.9), rs10805603 (OR=0.6, 95% CI=0.4-0.9), and rs1587607 (OR=0.7, 95% CI=0.5-1.0). PRLR SNP rs249522 was associated with increased risk of cancer in the additive model (OR=1.8, 95% CI =1.2-2.7). Minor allele carriers of the PRL SNP rs12210179, located in a putative transcription factor binding site, had a decreased risk of cancer in the additive model (OR=0.7, 95% CI=0.5-0.9). Conclusion: These data suggest that genetic variation in PRL and PRLR are associated with breast cancer in a population with a strong family history of breast cancer. Citation Format: Shehnaz K. Hussain, Mary Sehl, Daniel Conn, Janet S. Sinsheimer, Uma Dandekar, Jeanette Papp, Zuo-Feng Zhang, Patricia A. Ganz. Variation in the prolactin and prolactin receptor genes and familial breast cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A107.