Abstract P3-07-11: Nipple aspiration fluid yielders and non-yielders: Genetic characteristics

Abstract

Abstract Background: Nipple aspiration fluid (NAF) is a noninvasively acquired biosample that can provide a window of observation into the breast environment, but NAF yield is variable across studies, and is related to a variety of demographic and reproductive factors. We have recently observed a positive correlation between serum prolactin level and NAF yield status. The genetic traits determining NAF yield are unknown, but data from the 1970s linked wet type ear wax to NAF yield, and recent studies point to single nucleotide polymorphisms (SNPs) in the ABCC11 gene as a determinant of earwax type. Further, prolactin and prolactin receptor SNPs are related to serum prolactin level. We have investigated associations between NAF yield and SNPs in prolactin, prolactin receptor and ABCC11 genes in a recently completed case-control study. Method: NAF and/or blood were collected from 916 women. Subjects were defined as yielder if NAF volume was equal or more than 2μL and non-yielder if it was less than 2μL. According to this definition, our subjects categorized as 557 yielders and 359 non-yielders. DNA was extracted from blood using Qiagen kit and 20 ng of DNA was used to amplify and genotype for ABCC11 (rs17822931), PRLR (rs37364), PRL (rs2244502), PRL (rs849872) SNPs using Taqman genotyping assay on an Applied Biosystems 7900HT machine. Results: The median age of Yielders and Non-yielders was 51 and 54, respectively, with the same range of 31-70 for both groups (P<0.0001). There were 209(38%) premenopausal, 257(46%) postmenopausal and 81(15%) perimenopausal of yielders vs. 99(28%) premenopausal, 229(64%) postmenopausal and 26(7%) perimenopausal of non-yielders (P<0.0001). ABCC11 genotype distribution was significantly different between yielders and non-yielders (P = 0.00163). However, genotype distribution was not significantly different for PRLR (rs37364), PRL (rs2244502) and PRL (rs849872). YNYTotalP (N vs. NY)ABCC11 (rs17822931)5413578980.00163CC437 (81%)269 (75%)706 TT5 (1%)16 (4%)21 CT99 (18%)72 (20%)171 PRLR (rs37364)5483599070.176GG89 (16%)43 (12%)132 TT272 (50%)181 (50%)453 GT187 (34%)135 (38%)322 PRL (rs2244502)5393588970.087AA73 (14%)32 (9%)105 TT233 (43%)155 (43%)388 AT233 (43%)171 (48%)404 PRL (rs849872)5433599020.102CC17 (3%)11 (3%)28 TT332 (61%)244 (68%)576 CT194 (36%)104 (29%)298 Conclusion: Our analysis demonstrates a correlation between ABCC11 (rs17822931) SNP and NAF yield status, with the major homozygous CC allele associated with NAF yielder and minor homozygous TT allele associated with non-yielder status. If NAF-based risk biomarkers are to be developed, a better understanding of the genetics of NAF yield is required. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-07-11.