Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Background: Cancer incidence and mortality rate is disproportionate among the racial/ethnic groups in the U.S. and higher in African Americans (AAs) due to a combination of genes and environmental factors. The difference in serum vitamin D3, 25(OH)D, concentration among racial groups is suspected to be one of the sources of cancer health disparities. Vitamin D has protective effects against several types of cancer, and vitamin D deficiency is more common among AAs than the European Americans (EAs). Genome-Wide Association Studies (GWAS) among EAs found vitamin D pathway gene (VDPG) variants associated with serum 25(OH)D level, but association between VDPG variants and serum 25(OH)D level has not examined in AAs. Here, we tested if thirty-nine VDPG variants are associated with serum 25(OH)D concentration. Samples and Methods: Nineteen variants in GC, VDR, CYP3A4, CYP2R1, and CYP24A1 were genotyped in a total of 462 AAs from Washington, D.C. and Chicago area. Twenty GWAS identified VDPG variants were genotyped in a subset of subjects (n=332). West Africa Ancestry (WAA) was estimated using STRUCTRE from 105 ancestry informative markers typed. Then, we tested for association adjusting for WAA, age, and skin color. Results: Eight GWAS identified SNPs (five in GC, one in CYP2R1, and two in DHCR7/NADSYN1) were associated with serum 25(OH)D levels and/or vitamin D deficiency. Among darker-skinned AAs, the VDR SNP rs11568820 (Cdx2), was significantly associated (P&lt;0.05) with the risk of vitamin D deficiency (&lt;20 ng/ml) (OR=1.94; CI 1.11-3.38). Conclusion: We found VDPG variants associated with serum 25(OH)D level and/or vitamin D deficiency in AAs. We also replicated the findings from a previous GWAS in EAs and found that the same variants were associated with serum 25(OH)D in AAs. Additional studies are necessary to assess whether these variants are associated with cancer risk. Impact: Increased attention is focused on the role of vitamin D in cancer risk. Our findings provide insights on the biological and environmental modifiers of serum vitamin D3 and will help guide future studies on the role of vitamin D in cancer in high risk populations such as AAs.</jats:p>
<jats:p>Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4481. doi:1538-7445.AM2012-4481</jats:p>