Abstract 3763: Calcium intake, CABP1 polymorphisms, and the risk of colorectal adenoma: Results from Tennessee Colorectal Polyp Study

Abstract

Abstract Background: High calcium consumption may confer a reduced risk of colorectal adenoma and cancer. This effect could differ by polymorphisms in the genes involved in calcium regulation. The calcium binding protein 1(CABP1) gene encodes a calbindin-D9k protein, an important component of calcium mediated cellular signal transduction. CABP1 express primarily in intestine, and increased levels of Calbindin-D9k in intestine were found to be correlated with calcium hyperabsorption. A recent study found that deletion of CABP1 and another gene had a significant effect on calcium processing under calcium-deficient conditions. These findings suggest the variations in CABP1 expression in intestine may explain some of the variability in calcium absorption. However, so far no study has evaluated genetic variations in CABP1 with the risk of colorectal adenoma. Objectives: In the current study, we first screened whether CABP1 variants or their interactions with calcium intake were associated with urinary calcium among 256 normal controls. Further, single-nucleotide polymorphisms (SNPs) were evaluated for their independent association and interactions with calcium intake in relation to colorectal adenoma risk. Methods: Included in the study were 958 adenoma cases and 909 controls from 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. Seven tagging SNPs in CABP1 were analyzed. Linear regression models were used to estimate the association between genotypes and urinary calcium level. Multivariate unconditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). Multiplicative interactions for gene-diet interactions were evaluated in logistic regression models by using likelihood ratio tests. Results: Although no SNPs were observed to be associated with urinary calcium levels, one SNP (rs7956304) was found to be significantly associated with risk of adenoma. In comparison to participants with the GG genotype, participants with GA had higher risk of colorectal adenoma (OR=1.29, 95% CI 1.03-1.61, P=0.027), while participants with the AA genotype had no appreciable difference in risk (OR=0.82, 95% CI 0.50-1.35, P=0.428). This SNP was not observed to interact with calcium intake. Conclusions: These findings suggest that genetic variations in CABP1 may affect the risk of colorectal adenoma. To the best of our knowledge, this study is the first to evaluate CABP1 polymorphisms in relation to the risk of adenoma. Our finding of a significant association is promising; however, the finding should be confirmed in future studies. 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 3763. doi:10.1158/1538-7445.AM2011-3763