Abstract 4466: Local regulation of steroid hormones in the breast is related to single nucleotide polymorphism of steroid metabolism genes

Abstract

Abstract Background: The pattern of steroid hormone levels in nipple aspirate fluid (NAF) significantly differs from systemic levels, but may be a better predictor of breast cancer risk than the systemic environment. We hypothesize that local production and clearance of estrogen precursors or estrogen in the breast is affected by genetic variation in the enzymes involved in steroid transport, biosynthesis, and metabolism, thereby contributing to breast cancer risk. We examined the effect of functional single nucleotide polymorphism (SNP) on the concentrations of the NAF steroid hormones, as compared to serum levels. Methods: NAF was collected from both the contralateral unaffected breast of breast cancer patients and controls (blinded study of 265 women). Selection criteria for SNPs were; 1) known/potential functional significance on activity of the resulting enzyme. 2) Expression in breast tissue. 3) Caucasian population frequency of the minor alleles. gDNA was extracted from the plasma buffy coat by a Qiagen kit, followed by TaqMan genotyping assays (Applied Biosystems). The NAF and serum level of estradiol (E2), estrone (E1), progesterone (P4), testosterone (T), androstenedione (A4), and dehydroepiandrosterone (DHEA) were measured by immunoassay. Hormone levels were compared across genotype groups using the ANCOVA in SAS (age-adjusted significance p < 0.05). Results: (See the Table) Conclusions: There is no data yet to show that NAF hormone content is related to breast cancer risk. This hypothesis will be tested in our on-going study. Locally regulated biosynthesis and clearance of hormones from the breast seems likely. Our data support such a phenomenon, since NAF correlations with functional enzyme SNPs are more frequent than with serum. The significant relationships between SNPs and NAF hormones, not seen with the same serum hormone, support the notion that they are determinants of breast cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4466. doi:1538-7445.AM2012-4466