Abstract 909: Calcium intake, CASR polymorphisms and phenotype, and the risk of colorectal adenoma: Results from Tennessee Colorectal Polyp Study
Authors: Zhu Xiangzhu , Shrubsole Martha J. , Ness Reid M. , Cai Qiuyin , Long Jirong , Chen Zhi , Deng Xinqing , Luo Jianfeng , Smalley Walter E. , Zheng Wei , Dai Qi 
Published: February 2011

Abstract
Background: A number of cohort studies and randomized trials suggest that high calcium consumption may confer a reduced risk of colorectal cancer. Results, however, have been inconsistent. It is possible that the calcium effect may differ by polymorphisms in the genes involved in calcium regulation. Calcium-sensing receptor (CASR) tightly regulates systemic calcium levels by sensing minor changes in extracellular calcium concentration. Studies have found that CaSR is expressed in the human colon epithelium and regulates epithelial proliferation and differentiation. It was also shown that luminal calcium inhibited colorectal tumors through CaSR. Four studies have thus far investigated the associations of CASR polymorphisms and haplotypes and their interactions with calcium intakes in relation to risk of colorectal cancer or adenoma. However, these studies have generated inconsistent results. Objectives: In the current study, we first screened whether CASR variants or their interactions with calcium intake were associated with urinary calcium phenotype among 233 normal controls. SNPs which were associated with phenotype were further evaluated for their independent association and interaction with calcium intake on colorectal adenoma risk. Methods: Included in the study were participants of the Tennessee Colorectal Polyp Study (TCPS), an ongoing colonoscopy-based case control study conducted in Nashville, TN. Genotyping was performed using the Affymetrix Human Mapping 500K array set for 666 cases and 751 controls. Twenty two tagging single-nucleotide polymorphisms (SNPs) for CASR were analyzed. Linear regression models (SAS MIXED procedure) were used to estimate association between genotypes and urinary calcium level. Multivariate unconditional logistic regression models were used to estimate the odds ratio (OR) and 95% confidence intervals (CI) for each SNP. Multiplicative interactions for gene-diet interactions were evaluated in logistic regression models by using likelihood ratio tests. Results: Eleven SNPs were significantly associated with urinary calcium levels. Among these 11 SNPs, 4 SNPs significantly interacted with calcium intake in association with risk of adenoma. The association of the genotypes with adenoma risk differed by high or low level of calcium intake. We are conducting additional genotyping assays and will present the updated results in the AACR meeting. Conclusions: These findings suggest that some genetic variations in CASR and/or their interactions with dietary calcium intake have significant functional impact on calcium reabsorption, in turn, affect the risk of colorectal adenoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 909.