Abstract 2132: Personalized prevention of colorectal rectal trial (PPCCT)

Abstract

Abstract We previously reported from the Tennessee Colorectal Polyp Study that high total intakes of calcium or magnesium may only be related to a reduced risk of colorectal adenoma or hyperplastic polyp when the calcium/magnesium intake ratio was below 2.8. Furthermore, we found that calcium/magnesium intake ratio significantly interacted with the common Thr1482Ile polymorphism (rs8042919, GA) 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 (<2.8). In a recent report from the Calcium Polyp Prevention Study, a large-scale randomized clinical trial of calcium supplementation, it was found that calcium treatment only significantly reduced colorectal adenoma recurrence risk when the baseline dietary calcium/magnesium intake ratio was under 2.6 and this effect modification by the calcium/magnesium ratio cannot solely be attributed to the baseline dietary intake in calcium or magnesium. It is possible for those with a high calcium/magnesium ratio, reducing the calcium/magnesium intake ratio may be helpful. We are funded by NCI (R01CA149633) to conduct a personalized intervention trial clinical trial among 240 colorectal polyp patients with a high calcium/magnesium intake ratio. We are testing 1) if reducing the calcium/magnesium through magnesium supplementation affects biomarkers related to colorectal carcinogenesis in rectal tissues; and 2) if the effects differ by TRPM7 genotype. As of November 16, 2013, we have enrolled at least 160 participants and we plan to complete the trial by the end of January, 2015. Thus the uniqueness of the trial includes 1) only target colorectal polyp patients 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. 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 have also measured lipid profile and blood pressure. We have obtained very promising preliminary findings. We will report updated findings in the presentation. The results from our study may ultimately help to develop personalized strategies to prevent the colorectal cancer. Citation Format: Qi Dai, Martha J. Shrubsole, Xinqing Deng, Xiangzhu Zhu, Eugene Shubin, Tiffany McCray, Wei Zheng, Harvey Murff, Douglas Seidner, Reid M. Ness, Chang Yu. Personalized prevention of colorectal rectal trial (PPCCT). [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 2132. doi:10.1158/1538-7445.AM2014-2132