Abstract LB-452: Genetic polymorphisms in the <i>TRPM7</i> gene and colorectal adenoma risk
Authors: Xinqing Deng, Martha J. Shrubsole, Reid M. Ness, Qiuyin Cai, Todd Edwards, Jirong Long, Zhi Chen, Yinghao Su, Xiangzhu Zhu, Pin Sun, Jianfeng Luo, Walter E. Smalley, Wei Zheng, Qi Dai
Journal: Cancer Research (2011)

Abstract Background: Several epidemiologic studies suggest that high magnesium intake is associated with reduced risk of colorectal cancer or colorectal adenoma. Results, however, have been inconsistent. Ionized magnesium (Mg2+) counters the action of ionized calcium (Ca2+) in many physiologic activities. We previously reported that the associations between intakes of magnesium, calcium or calcium/magnesium ratio with risk of colorectal polyp were modified by the common Thr1482Ile polymorphism in the gene for the transient receptor potential melastatin 7 (TRPM7), which is a ubiquitously expressed constitutive ion channel with a higher affinity for Mg2+ than for Ca2+ and plays a central role in magnesium homeostasis and magnesium (re)absorption pathways. Except for our earlier study, no other study has investigated these possible gene-nutrient interactions in the etiology of colorectal adenoma or cancer. In the present study, we examined single nucleotide polymorphisms (SNPs) in the TRPM7 gene and their interaction with calcium and magnesium intake or calcium/magnesium ratio in relation to risk of colorectal adenoma using data from the Tennessee Colorectal Polyp Study. Methods: Included in the study were participants of the Tennessee Colorectal Polyp study, an ongoing colonoscopy-based case control study conducted in Nashville, TN. Genotyping was performed at Vanderbilt Microarray Shared Resource using the Affymetrix Genome-Wide Human SNP Array 5.0. Sixteen SNPs in the TRPM7 gene were genotyped for 958 colorectal adenoma cases and 909 controls. Hardy-Weinberg equilibrium was assessed for each SNP among controls. The associations of each genotype with colorectal adenoma risk were evaluated under dominant, recessive and additive models, respectively. Multivariate unconditional logistic regression models were used to estimate the odds ratio and 95% confidence intervals for each SNP. Multiplicative interactions were evaluated for gene-diet interactions using likelihood ratio tests. Results: All the genotype frequencies for the TRPM7 were in Hardy-Weinberg equilibrium. Of the sixteen SNPs, Four SNPs were significantly associated with risk of colorectal adenoma whereas six SNPs significantly interacted with dietary calcium intake or the ratio of dietary calcium to magnesium intake (five SNPs with calcium and six with the ratio) in relation to risk of colorectal adenoma. The two sets of SNPs were not in strong linkage disequilibrium (LD). However, either three of the four associated SNPs or all of the six interacting SNPs were in strong LD with one another respectively. No significant interactions with magnesium intake were observed. Conclusions: Our results suggest that genetic polymorphisms in the TRPM7 gene, particularly their interactions with calcium or calcium/magnesium ratio, contribute to risk of colorectal adenoma. Further replications in large-scale studies are ongoing. 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 LB-452. doi:10.1158/1538-7445.AM2011-LB-452