Abstract 4478: Erythrocyte magnesium, <i>TRPM7</i> Thr1482Ile polymorphism, and colorectal adenoma risk
Authors: Xinqing Deng, Martha J. Shrubsole, Reid M. Ness, Qiuyin Cai, Xiangzhu Zhu, Walter E. Smalley, Todd L. Edwards, Wei Zheng, Qi Dai
Journal: Cancer Research (2012)

Abstract Background: Several epidemiologic studies indicate high intake of magnesium may be related to a reduced risk of colorectal cancer and adenoma. However, results from previous studies have not been consistent. We reported previously the inverse association between dietary magnesium and risk of colorectal adenoma primarily appeared in those who carried at least one Thr1482Ile allele in the transient receptor potential melastatin 7 (TRPM7) gene, which plays an essential role in the homeostasis and sensing of magnesium. Serum magnesium is regulated in a narrow range and previous studies indicate erythrocyte magnesium may be a better biomarker of body magnesium status than serum magnesium. Objective: To examine whether erythrocyte magnesium is associated with adenoma risk and if the association is modified by the Thr1482Ile polymorphism. Design: Included in this nested case-control study were 341adenoma cases and 343 matched polyp-free controls from the Tennessee Colorectal Polyp Study (TCPS), a colonoscopy-based case control study conducted in Nashville, TN. Total erythrocyte magnesium levels were measured using flame atomic absorption spectroscopy. Genotyping assay was performed using the TaqMan OpenArray platform. Multivariate logistic regression models were used to estimate the odds ratio and 95% confidence intervals as a measure of the strength of associations. The association of each genotype with colorectal adenoma risk was evaluated under dominant, recessive and additive models, respectively. Results: Overall erythrocyte magnesium level was not associated with risk of colorectal adenoma. However, erythrocyte magnesium tended to be associated with a reduced risk among those who carried at least one Thr1482Ile allele in the TRPM7 gene (rs8042919), particularly after adjusting for potential confounding factors, such as age, assay batch, family history, and dietary intakes of magnesium and fiber with the ORs (95% CI) of 0.19 (0.05, 0.76) and 0.34 (0.08, 1.49) respectively for the medium and highest tertile of erythrocyte magnesium levels versus the lowest tertile. In addition, among people with erythrocyte magnesium below the median, we found people who carried at least one 1482Ile allele tended to be at an elevated risk of adenoma with an OR (95% CI) of 1.7(0.85, 3.43), compared to those who did not carry the polymorphism; while the corresponding OR (95% CI) was 0.94 (0.49, 1.81) for those who carried at least one Thr1482Ile allele if erythrocyte magnesium was above the median. Conclusions: Our findings indicate the TRPM7 Thr1482Ile polymorphism may interact with erythrocyte magnesium levels in relation to colorectal adenoma risk even after controlling for dietary intake of magnesium. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4478. doi:1538-7445.AM2012-4478