Association of calcium and vitamin D intake and vitamin D receptor genotypes with prostate cancer in multiethnic samples
Abstracts: Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; November 9-12, 2014; San Antonio, TX
Cancer Epidemiol Biomarkers Prev October 2015 24; B16, doi: 10.1158/1538-7755.DISP14-B16
Ken Batai1, Adam B. Murphy2, Ebony Shah1, Maria Ruden3, Jennifer Newsome4, Michael A. Dixon2, Ahaghotu Chiledum5, and Rick A. Kittles1
1University of Arizona, Tucson, AZ,
2Northwestern University, Chicago, IL,
3University of Chicago, Chicago, IL,
4University of Illinois at Chicago, Chicago, IL,
5Howard University Hospital, Washington, DC.
Calcium > 800 mg associated with 2X HIGHER aggressiveness, even worse with AA
Vitamin D > 600 IU associated with 2X LOWER aggressiveness
Background: Prostate cancer (PCa) is the most common cancer among men in the U.S., and African American (AA) men have higher incidence and mortality rate compared to European American (EA) men. Social and behavioral factors affect stage and tumor grade at diagnosis, treatment choice, and mortality. However, the cause for PCa disparities is still unclear. Several roles have been proposed for calcium, vitamin D, and the vitamin D receptor (VDR) in PCa pathogenesis and progression, but epidemiologic studies, mainly conducted in European descent populations, often show inconsistent evidence of associations. Here, we investigated the association of calcium and vitamin D intake and VDR genotypes with prostate cancer incidence and aggressiveness in multiethnic samples.
Methods: The total of 1,403 individuals was included in this study (751 AAs, 481 EAs, 126 Hispanic Americans, and 45 others). Study participants were recruited from six hospitals in Chicago, IL and Washington, D.C. Calcium and vitamin D intake was evaluated using the Block calcium and vitamin D screener. Seven single-nucleotide polymorphisms (SNPs) in and around the VDR gene and 105 ancestry informative markers were genotyped. STRUCTURE was used to estimate genetic ancestry. We performed logistic regression analyses adjusting for relevant variables using SPSS.
Results: In the pooled data set, calcium and vitamin D intake was not associated with PCa risk (P>0.05), but high total calcium intake (≥800 mg/day) was significantly associated with aggressive PCa (Gleason Score ≥4+3, P=0.002, OR=2.05, 95% C.I.: 1.29-3.26). In the race/ethnicity stratified analyses, we confirmed the statistically significant associations of calcium intake with aggressive PCa in Aas.
High total vitamin D intake (≥600IU/day), on the other hand, revealed a protective effect against aggressive PCa (OR=0.47, 95% C.I.: 0.24-0.92, P=0.026). In EAs, total calcium intake was significantly associated with PCa aggressiveness, only when we compared PCa cases with Gleason Score ≥4+3 to cases with Gleason Score <4+3 (P=0.047, OR=2.52, 95% C.I.: 1.01-6.27). In AAs, the G allele of rs11568820 (Cdx2) had a protective effect, and AG/GG genotype was strongly associated with high risk PCa (P=0.014, OR=0.35, 95% C.I.: 0.15-0.81). In EAs, rs73136 (TaqI) C allele and rs1544410 (BsmI) G allele showed a protective effect against aggressive PCa. TaqI CT/CC genotypes had odds ratio of 0.40 (95% C.I.: 0.18-0.91, P=0.03), and the odds ratio for BsmI AG/GG genotypes was 0.33 (95% C.I.: 0.14-0.76, P=0.009) in EAs. We also observed evidence of interactions between Cdx2 genotypes and total calcium intake and between rs11574143 genotype and total calcium intake in AAs. Significant interactions were also observed between TaqI genotype and total calcium intake in EAs.
Conclusion: In this study, we showed that high calcium intake increases the risk of prostate cancer aggressiveness, while high vitamin D intake has protective effects. Although a larger sample size is necessary to confirm the observation, we demonstrated that VDR genotypes may modify the effect of calcium intake. The findings from this study may help develop better PCa management plans.
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