Calcium/magnesium intake ratio, but not magnesium intake, interacts with genetic polymorphism in relation to colorectal neoplasia in a two-phase study

Xiangzhu Zhu, Martha J. Shrubsole, Reid M. Ness, Elizabeth A. Hibler, Qiuyin Cai, Jirong Long, Zhi Chen, Guoliang Li, Ming Jiang, Lifang Hou, Edmond K. Kabagambe, Bing Zhang, Walter E. Smalley, Todd L. Edwards, Edward L. Giovannucci, Wei Zheng, Qi Dai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Some studies suggest that the calcium to magnesium ratio intakes modify the associations of calcium or magnesium with risk of colorectal adenoma, adenoma recurrence, and cancer. Parathyroid hormone (PTH) plays a key role in the regulation of homeostasis for both calcium and magnesium. We hypothesized that polymorphisms in PTH and 13 other genes may modify the association between the calcium/magnesium intake ratio and colorectal neoplasia risk. We conducted a two-phase study including 1336 cases and 2891 controls from the Tennessee Colorectal Polyp Study. In Phase I, we identified 19 SNPs that significantly interacted with the calcium/magnesium intake ratio in adenoma risk. In Phase II, rs11022858 in PTH was replicated. In combined analysis of phases I and II, we found high calcium/magnesium intake ratio tended to be associated with a reduced risk of colorectal adenoma (P for trend, 0.040) among those who carried the TT genotype in rs11022858. In stratified analyses, calcium intake (≥ 1000 mg/d) was significantly associated with 64% reduced adenoma risk (OR = 0.36 (95% CI : 0.18–0.74)) among those homozygous for the minor allele (TT genotype) (P for trend, 0.012), but not associated with risk in other genotypes (CC/TC). Conversely, we found that highest magnesium intake was significantly associated with 27% reduced risk (OR = 0.73 (95% CI : 0.54–0.97)) of colorectal adenoma (P for trend, 0.026) among those who possessed the CC/TC genotypes, particularly among those with the TC genotype, whereas magnesium intake was not linked to risk among those with the TT genotype. These findings, if confirmed, will help for the development of personalized prevention strategies for colorectal cancer.

Original languageEnglish (US)
Pages (from-to)1449-1457
Number of pages9
JournalMolecular Carcinogenesis
Volume55
Issue number10
DOIs
StatePublished - Oct 1 2016

Funding

This study was supported through the US National Center for Complementary and Alternative Medicine grants R01AT004660, Office of Dietary Supplements, National Cancer Institute grants R01CA149633 (to QD) and U01CA182364 (to QD & TLE), as well as parent studies P50CA95103 (to WZ) and R01CA121060 (to WZ) and the American Institute for Cancer Research Grant #08A074 (to QD). The survey and sample processing for the TCPS were conducted by the Survey and Biospecimen Shared Resource supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA68485). Additional support was provided by the Vanderbilt Clinical and Translational Research Scholar award (5KL2RR024975) (to TLE). We wish to thank Regina Courtney for her excellent laboratory technical support.

Keywords

  • PTH
  • calcium
  • colorectal neoplasia
  • gene-nutrient interaction
  • magnesium

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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