Abstract PR-3: CDX-2 polymorphism, calcium intake, and prostate cancer risk for African Americans in a population-based study

Abstract

Abstract Background: Prostate cancer incidence and mortality rates are highest among American men of African descent. The World Cancer Research Fund has classified calcium as a probable cause of prostate cancer. The CDX-2 polymorphism (A to G) in the Vitamin D Receptor (VDR) alters calcium absorption in the small intestines. It functionally limits transcriptional activity of the VDR promoter. VDR impacts cell differentiation, metastasis, and apoptosis in the prostate. The CDX-2 polymorphism is potentially useful for determining whether prostate cancer risk is causally related to calcium absorbing activity. Methods: To study the impact of calcium intake and absorption among our most at-risk ethnic group, we examined 447 African American cases (233 advanced stage at diagnosis; 214 localized) and controls (N=223) from the California Collaborative Study of Aggressive Prostate Cancer. Using DNA extracted from buffy coat, the VDR CDX-2 genotype was measured by TaqMan assay. Dietary calcium was assessed from a 74-item modified Block food frequency questionnaire. Main effects of genotype and of dietary calcium, and diet-gene interactions were estimated using conditional logistic regression, adjusting for SES, age, family history, and total caloric intake. Results: Men who were least able to absorb calcium (GG genotype) were at 59% decreased risk of advanced prostate cancer; the adjusted relative risk was OR=0.41 (95% confidence interval =0.19, 0.90). Men with high total calcium intake (in the upper quartile) had an approximate two-fold increased risk of advanced prostate cancer compared to those in the lowest quartile; all cases OR= 1.91 (95% CI=1.20,3.03); OR=2.16 (95% CI= 1.26,3.71) for advanced stage. The dose-response relationship was significant (P-value for trend < 0.01). Gene by Nutrition interactions were not significant. Conclusions: Our findings provide evidence that African American carriers of the ancestral CDX-2 ‘AA’ allele for enhanced biological absorption of calcium, are at high risk for aggressive prostate cancer; and that high intake of dietary or total calcium poses formidable risks for both advanced and localized prostate cancer. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):PR-3.