Abstract 5593: Are variants in the syndecan-1 gene associated with breast cancer risk in older women

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Syndecans are transmembrane proteins on the cell surface that act as receptors for ligands from a number of protein families. These proteoglycans are involved in a large number of important normal cell functions, including signaling, proliferation, and cell-matrix adhesion; they are also involved in aberrant cell functions such as inflammation, angiogenesis, and carcinogenesis. In a recent pathway directed re-analysis of GWAS data (Menashe, Cancer Research, 2010), variants in the syndecan-1 (SDC1) gene on chromosome 2p were found to be associated with excess risk of breast cancer. We sought to extend this finding by investigating the association between tagging SNPs in the SDC1 gene and risk of breast cancer in our case-control study (The PACE study) in older women. This population-based study includes 845 women who were 65-79 years old at diagnosis of incident breast cancer and 807 age-matched unaffected controls from the Seattle area. The analysis was restricted to Caucasian women. A total of 11 SNPs were chosen to represent 10 bins using Snagger, with double coverage of one large bin. Five SNPs failed genotyping, leaving six SNPs for analysis. At the gene level, a P-min permutation test was not significant for SDC1 (p=0.10). Three SNPs, rs10495704, rs2002090, and rs3771240, were in high linkage disequilibrium in our controls (r2 0.81-0.87) and all three were separately associated with marginally increased risks of breast cancer (OR 1.2, 95% CI 1.0-1.4). One of these SNPs, rs10495704, is in the 5’UTR and thus could be associated with protein processing. No excess risk of breast cancer was associated with the other three SDC1 variants: rs4432408, rs2348478, or rs2015110. A similar pattern of marginally increased risk for the three polymorphisms in high LD (rs10495704, rs2002090, and rs3771240) was found in two subsequent analyses restricted to women with ductal histology and luminal type tumors. We are currently assessing other genes related to inflammation that may be related to breast cancer risk in this study population. The data for SDC1 in the PACE study cannot rule out a modest association with breast cancer risk. 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 5593. doi:10.1158/1538-7445.AM2011-5593