Abstract 5595: Polymorphisms in metastasis suppressor genes (BRMS1 and SIPA1): Breast tumor characteristics and lymph node metastasis
Authors: Roberts Michelle , Hong Chi-Chen , Edge Stephen , Yao Song , Nesline Mary , Ambrosone Christine B. 
Published: June 2012

Abstract
Introduction: BRMS1 and SIPA1 function as metastasis suppressors, but few studies have examined metastasis suppressor gene polymorphisms in breast cancer. Axillary lymph node (LN) metastases and tumor characteristics predict aggressiveness but correlate imperfectly with likelihood of metastatic relapse. BRMS1 regulates transcription through NF-κB pathways; protein expression has been correlated with ER/PR negative, HER2 positive tumors. SIPA1 affects extracellular matrix gene expression, and polymorphisms have been associated with LN metastases and ER/PR negative tumors. Identifying polymorphisms that affect metastasis may help to better recognize patients who require aggressive adjuvant therapy. We assessed associations between SNPs in BRMS1 and SIPA1 and LN metastases, tumor grade, and ER/PR/HER2 status in breast cancer patients. Methods: We included 1,015 newly diagnosed breast cancer patients who received surgery at Roswell Park Cancer Institute (RPCI) and participated in the DataBank and BioRepository shared facility. Participants completed an epidemiologic questionnaire and provided a blood sample prior to surgery or other treatment. Clinical and pathologic data were linked to de-identified participant data in the DBBR database. BRMS1 (rs11537993 and rs3116068) and SIPA1 (rs75894763) SNPs were genotyped through RPCI's Genomics shared facility using Sequenom® iPLEX Gold assays. Logistic regression was used to estimate odds ratios and 95% confidence intervals. Results: Tumors were more frequently node positive among never-users of hormone replacement therapy, and node positive tumors were more likely to be high grade, ER/PR negative, and HER2 positive. Node positive disease was less likely among patients heterozygous for BRMS1 rs3116068 (OR=0.76, 95% CI=0.55-1.05) and SIPA1 rs75894763 (OR=0.42, 95% CI=0.16-1.09). BRMS1 rs11537993 was not associated with lymph node metastases. The SIPA1 rs75894763 variant allele was also associated with reduced risk of ER and PR negative tumors. HER2 positive tumors were more likely among patients homozygous for BRMS1 rs3116068 (OR=2.38, 95% CI=1.15-4.94). No significant associations with tumor grade were observed. Conclusions: Preliminary data indicate that polymorphisms in BRMS1 and SIPA1 are associated with ER, PR, and HER2 tumor status, and with reduced risk of LN involvement among breast cancer patients. Future research to evaluate these and other genetic variants in metastasis suppressor genes in relation to recurrence and survival is necessary to better understand the biology of metastasis.
This research was supported by a gift from the Jayne and Phil Hubbell Family. The DBBR and Genomics Facility are RPCI Cancer Center Support Grant shared resources, supported by P30 CA016056-32. Ms. Roberts is a DOD Predoctoral Award recipient (BC10068) and Dr. Ambrosone is funded by the Breast Cancer Research Foundation.
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 5595. doi:10.1158/1538-7445.AM2011-5595