Abstract A18: Personalized prevention of colorectal cancer trial

Background: High calcium or high magnesium consumption has been linked to reduced risks of colorectal adenoma and cancer. However, results are not consistent. In the Tennessee Colorectal Polyp Study (TCPS), the Calcium Polyp Prevention Study (a large-scale randomized trial), we found that high intake of supplemental calcium or total calcium was related to a reduced risk of colorectal adenoma or adenoma recurrence only among those with calcium/magnesium intake ratio below 2.8 or 2.6. This effect modification by the calcium/magnesium ratio cannot solely be attributed to the dietary intake in calcium or magnesium. Furthermore, we found in the TCPS that calcium/magnesium intake ratio significantly interacted with Thr1482Ile polymorphism (rs8042919, GaA) in the TRPM7 gene, in relation to both adenomas and hyperplastic polyps. The TRPM7 gene is involved in magnesium and calcium re(absorption) and homeostasis. Compared to those with the GG genotype, we found that people who carry A allele(s) were at 60% and 85% increased risks of adenoma and hyperplastic polyp, respectively, if they also consumed diets with calcium/magnesium intake ratio >2.8; and the corresponding risks increased by 345% and 1500% among those with the AA genotype. The risk was not increased among those who carried the A allele(s) if they consumed diets low in calcium/magnesium ratio ( Objectives: 1) Test the hypothesis whether reducing the calcium/magnesium through magnesium supplementation affects biomarkers related to colorectal carcinogenesis in rectal tissues; and 2) Test whether the effect differs by TRPM7 genotype. Methods: Personalized Prevention of Colorectal Cancer Trial (PPCCT, R01CA149633) is an ongoing double-blind, randomized trial of 12 week personalized magnesium supplementation. 288 participants with high calcium/magnesium intake ratio and at high risk of colorectal cancer are being recruited. The uniqueness of the trial includes 1) only target participants with a high calcium/magnesium ratio through nutritional screening using multiple 24-hour dietary recalls; 2) personalized doses are based on and used to reduce the current calcium/magnesium intake ratios; and finally, 3) the participants are also randomized by the TRPM7 genotype. Results: As of July 20, 2014, we have enrolled at least 170 participants. We have conducted immunohistochemical assays to measure expressions of carcinogenesis biomarkers, including apoptosis, cell proliferation, COX2 and TRPM7, in normal rectal tissues collected at baseline and the end of the intervention for 40 participants who first completed the trial. We are also assaying lipid profile and other novel biomarkers, including DNA methylation, and microbial markers. We have obtained some very promising preliminary findings. We will report updated findings in the presentation. Conclusions: The results from our study may ultimately help to develop personalized strategies to prevent colorectal cancer. Citation Format: Xiangzhu Zhu Zhu, Chang Yu, Martha J. Shrubsole, Xinqing Deng, Eugene Shubin, Jennifer M. Engle, Wei Zheng, Harvey J. Murff, Douglas L. Seidner, Reid M. Ness, Qi Dai. Personalized prevention of colorectal cancer trial. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A18.