Calcium, vitamin D, VDR genotypes, and epigenetic and genetic changes in rectal tumors.
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.
Slattery
Martha L
ML
University of Utah, Salt Lake City, Utah 84108, USA. marty.slattery@hsc.utah.edu
Wolff
Roger K
RK
Herrick
Jennifer S
JS
Caan
Bette J
BJ
Samowitz
Wade
W
D000328:Adult; D000368:Aged; D002136:Calcium, Dietary / Q000032:analysis*; D016022:Case-Control Studies; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D016158:Genes, p53; D056726:Genetic Association Studies; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018167:Receptors, Calcitriol / Q000235:genetics*; D012004:Rectal Neoplasms / Q000235:genetics*; D013472:Sunlight; D011795:Surveys and Questionnaires; D014481:United States; D014807:Vitamin D / Q000008:administration & dosage*; D018631:ras Proteins / Q000235:genetics
D002136:Calcium, Dietary; D004273:DNA, Neoplasm; D005819:Genetic Markers; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D018167:Receptors, Calcitriol; D014807:Vitamin D; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins