Abstract 2196: Two-phase study ofPTHpolymorphisms, calcium, magnesium and colorectal adenoma risk

Background: The findings on the associations between intakes of calcium and magnesium with risks of colorectal adenoma and cancer have not been consistent. Previous studies identified substantial inter-person variability in calcium absorption (10-70%). The differences in calcium absorption persist over time and only a small portion of cases can be explained by known factors. Calcium competes with magnesium in many biological activities such as (re)absorption. The polymorphisms in genes related to calcium and magnesium may modify the associations between intakes of calcium and magnesium and risk of colorectal cancer and adenoma. Parathyroid hormone (PTH) is a critical hormone in the regulation of calcium concentration and magnesium in extracellular fluid and plays a key role in (re)absorption of both calcium and magnesium in the gut and kidney. Objectives: We hypothesize that common variants in PTH may modify the associations between calcium and magnesium intake or calcium/magnesium ratio and risk of colorectal adenoma risk. Methods: Included were participants of the Tennessee Colorectal Polyp Study (TCPS), a colonoscopy-based case control study conducted in Nashville, TN. In the Phase I study, genotyping was performed using the Affymetrix Human Mapping 500K array in 728 colorectal adenoma cases and 757 controls and 3 tagging single-nucleotide polymorphisms (SNPs) in the PTH gene were evaluated. SNPs identified as significant in phase I were genotyped in Phase II in an independent set (546 cases and 2062 controls). Dietary nutrient intakes were obtained from a food frequency questionnaire. Multivariate unconditional logistic regression models were used to estimate the odds ratios and 95% confidence intervals for each SNP. Multiplicative interactions were evaluated for gene-diet interactions using likelihood ratio tests. Results: In Phase I of the study, we identified 2 SNPs that significantly interacted with calcium to magnesium (Ca/Mg) intake ratio in association with adenoma risk. In an independent set (Phase II), one of two gene-Ca/Mg ratio interactions was replicated. In the combined analysis, we found that intakes of calcium and magnesium were related to a reduced risk of colorectal adenoma. However, in stratified analysis, magnesium intake was only associated with a reduced risk of adenoma among those with the TC/CC genotype (p for trend, 0.03). Magnesium intake≥320 mg/day was linked to about 40% reduction in risk among those with the TC genotype. On the other hand, calcium intake was only related to a reduced risk for those who carry the TC/TT genotype (p for tend, 0.02). Calcium intake≥1000 mg/day was associated with an over 40% reduction in risk of colorectal adenoma among the TT group. Conclusions: Intakes of calcium and magnesium are linked to reduced risk of adenoma for subsets of populations with different genotypes. Citation Format: Zhu Xiangzhu, Martha J. Shrubsole, Reid M. Ness, Qiuyin Cai, Walter E. Smalley, Todd L. Edwards, Edward Giovannucci, Wei Zheng, Qi Dai. Two-phase study of PTH polymorphisms, calcium, magnesium and colorectal adenoma risk. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2196. doi:10.1158/1538-7445.AM2014-2196