Abstract 2611: Role of circadian genes in breast cancer: Analysis of the CECILE study, a population-based case-control study conducted in France

Abstract

Abstract Breast cancer risk has been associated with shift work and light exposure at night. It has been suggested that disruption of circadian rhythms induced by these exposure may play a role in tumorigenesis. Circadian rhythms regulate diverse physiologic processes, including regulation of sex hormone levels, and genes controlling the circadian rhythm were found to regulate cell proliferation, cell cycle regulation and apoptosis. However, only few studies have investigated the role of these genes in breast cancer. The purpose of this study was to analyze the association between polymorphisms in circadian genes and breast cancer risk. The CECILE study is a population-based case-control study on environmental and genetic factors. A total of 1135 incident cases and 1167 controls provided DNA samples. We genotyped 570 tagging and functional SNPs from the 22 genes in the circadian rhythm pathway defined by KEGG. Preliminary results based on a SNP by SNP analysis using unconditional logistic regression highlighted 36 SNPs with p-value<0.05 in RORA, CUL1, NPAS2, CRY1, CRY2 and CLOCK genes. Of these, 3 SNPs in RORA were significantly associated with breast cancer after Bonferroni correction for multiple testing (p<0.0001). In ongoing analyses, we use the Multilevel Inference for SNP Association (MISA) method, which is a more powerful method that allows estimating associations at the SNP, gene and pathway level. These analyses will be presented. Our results suggest a role of the circadian gene in breast cancer risk. Further analysis on possible interaction between shift work and genetic variants highlighted in this study in relation to breast cancer risk will be conducted in the CECILE study. 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 2611. doi:1538-7445.AM2012-2611