Abstract
Calcium, vitamin D, exposure to sunshine, and vitamin D receptor (VDR) genotypes have been associated rectal cancer. We used data from 750 rectal tumors and 1,205 population-based controls examine associations with TP53, KRAS2, and CpG Island methylator phenotype (CIMP) markers. Rectal tumors were associated with high levels of calcium overall and with TP53 tumor mutations specifically (OR = 0.6, 95% CI = 0.42–0.84). High levels of sunshine exposure had a borderline protective effect for TP53 tumor mutations (OR = 0.78, 95% CI = 0.59–1.03). A mutation at codon 248 was significantly associated with dietary calcium intake (OR = 0.26, 95% CI = 0.09–0.77); having the Ff/ff genotypes of the FOK1 VDR polymorphism significantly increased the odds of a mutation at codon 245 (OR = 4.74, 95% CI = 1.05–21.39); high levels of dietary vitamin D (OR = 3.42, 95% CI = 1.15–10.17) and the Ff/ff genotypes of FOK1 (OR = 3.34, 95% CI = 1.11–10.02) and the GA/AA genotypes of the CDX2 VDR polymorphism (OR = 2.85, 95% CI = 1.23–6.58) increased the odds of a TP53 mutation at codon 273. These data support an association between calcium and rectal tumors overall as well as specifically with TP53 mutations. However, given the number of comparisons, findings need to be confirmed in other studies.
ACKNOWLEDGMENTS
This study was funded by grants CA48998 and CA61757 to M. L. Slattery. This research was supported by the Utah Cancer Registry, which is funded by Contract #N01-PC-67000 from the National Cancer Institute, with additional support from the State of Utah Department of Health and the University of Utah, the Northern California Cancer Registry, and the Sacramento Tumor Registry. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official view of the National Cancer Institute. We would like to acknowledge the contributions of Sandra Edwards, Leslie Palmer, and Judy Morse to the data collection and management efforts of this study and to Erica Wolff and Michael Hoffman for genotyping, sequencing, and methylation analysis.