Background: 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 single-nucleotide polymorphism (SNP) in the CDX-2 binding site of the vitamin D receptor (VDR) gene, among African American men. Methods: 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. OR were estimated using conditional logistic regression. Results: Among both Blacks and Whites, we observed a threshold for calcium intake (604 mg/d) 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/d) had a 50% reduction in risk as compared with those in the upper three quartiles [OR = 0.49; 95% confidence interval (CI), 0.36-0.67]. The association between calcium intake and prostate cancer risk was not modified by genotype at other VDR loci. Conclusions: Our findings support the hypothesis that genetic determinants of calcium absorption influence prostate cancer risk. Impact: The differences between African Americans and Whites in calcium absorption and dietary calcium intake may contribute to racial disparities in prostate cancer incidence and mortality rates.
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