Abstract 3758: The relationship of calcium and magnesium intakes, VDR polymorphisms and the risk of colorectal adenoma: results from the Tennessee Colorectal Polyp Study

Abstract

Abstract Background: Epidemiological studies suggest that high calcium intake and adequate vitamin D levels may reduce risk of colorectal cancer or adenoma although findings have not been entirely consistent. Some previous studies found that the association between calcium intake and colorectal cancer or adenoma was modified by polymorphisms in vitamin D receptor (VDR) gene. In addition to regulating calcium level, vitamin D is also involved in magnesium homeostasis. However, no study has investigated possible interaction between magnesium intake and VDR polymorphisms. Objectives: To investigate whether intakes of calcium, particularly magnesium, interact with VDR genetic variants in relation to colorectal adenoma risk. Methods: Included in the study are 958 adenoma cases and 909 healthy 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. Dietary nutrients intakes were obtained from food frequency questionnaire (FFQ) and dietary supplements and adjusted for total energy intake using the residual method. Multivariate unconditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). Multiplicative interactions for gene-nutrients interactions were evaluated in logistic regression models by using likelihood ratio tests. Results: Eighteen tagging SNPs in the VDR gene were analyzed. Two SNPs (rs12717991, rs2189480) were significantly associated with a reduced risk of colorectal adenoma. Furthermore, intakes of calcium (p for interaction, 0.01) and magnesium (p for interaction, 0.03) significantly interacted with rs2189480 in relation to adenoma risk. The inverse association with rs2189480 was of borderline significance among participants with a low calcium intake (P for trend=0.06) with ORs (95% CI) of 0.80 (0.58, 1.10) and 0.67 (0.41, 1.10), respectively, for GT and TT. Among participants with high intake of magnesium, the inverse association was significant (P for trend=0.007) with ORs (95%CI) of 0.52 (0.38, 0.72) and 0.72 (0.44, 1.18), respectively for GT and TT. Conclusions: These findings suggest that some genetic variations in the VDR gene may interact with dietary intakes of calcium and magnesium intake in the risk of colorectal adenoma. 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 3758. doi:10.1158/1538-7445.AM2011-3758