Protective effects of low calcium intake and low calcium absorption vitamin D receptor genotype in the California Collaborative Prostate Cancer Study
Published Date:Nov 05 2012
Source:Cancer Epidemiol Biomarkers Prev. 22(1):16-24.
Dose-Response Relationship, Drug
European Continental Ancestry Group
Polymorphism, Single Nucleotide
Vitamin D Receptor
Pubmed Central ID:PMC3763955
Funding:1U58DP000807-3/DP/NCCDPHP CDC HHS/United States
N01-PC-35136/PC/NCI NIH HHS/United States
N01-PC-35139/PC/NCI NIH HHS/United States
R01 CA084979/CA/NCI NIH HHS/United States
R01CA84979/CA/NCI NIH HHS/United States
T32-CA009492/CA/NCI NIH HHS/United States
High calcium intake is consistently associated with increased prostate cancer risk in epidemiologic studies. We previously reported that the positive association between calcium intake and risk of aggressive prostate cancer was modified by the Vitamin D Receptor (VDR) calcium absorption genotype, Cdx2, among African American men.
We expanded our previous study to include White men, a population with a higher calcium intake and a higher prevalence of the low absorption allele. We also examined VDR polymorphisms at other loci unrelated to calcium absorption. The study included 1,857 prostate cancer cases (1,140 with advanced stage at diagnosis, 717 with localized stage) and 1,096 controls. Odds ratios (OR) were estimated using conditional logistic regression.
Among both Blacks and Whites, we observed a threshold for calcium intake (604 mg/day) below which prostate cancer risk declined sharply. Low calcium intake was most strongly associated with decreased risk among men with the VDR Cdx2 low calcium absorption genotype (p for interaction = 0.001 and p=0.06 for Whites and African Americans, respectively). Among all men with this genotype, those in the lowest quartile of calcium intake (<=604 mg/day) had a 50% reduction in risk compared to those in the upper three quartiles (OR=0.49, 95% CI=0.36–0.67). The association between calcium intake and prostate cancer risk was not modified by genotype at other VDR loci.
Conclusions and Impact
Our findings support the hypothesis that genetic determinants of calcium absorption influence prostate cancer risk and may contribute to racial disparities in prostate cancer incidence and mortality rates.
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