Polymorphic Variation in theGCandCASRGenes and Associations with Vitamin D Metabolite Concentration and Metachronous Colorectal Neoplasia
Year: 2012
Type: article
Abstract: BACKGROUND: Vitamin D levels and calcium intake have been associated with risk of colorectal neoplasia, and genetic variation in vitamin D pathway genes may affect circulating vitamin D metabolite concentrations and/or risk for colorectal lesions. This study evaluated associations between polymorphic variation in the Gc-globulin (GC) and calcium-sensing receptor (CASR) and odds for metachronous colorectal neoplasia and vitamin D metabolite concentrations. METHODS: Participants from the Ursodeoxycholic Acid (UDCA) and Wheat Bran Fiber (WBF) trials (n = 1,439) were analyzed using a single-nucleotide polymorphism (SNP) tagging approach, with a subset (n = 404) of UDCA trial participants for whom vitamin D metabolite concentrations were also available. A total of 25 GC and 35 CASR tagSNPs were evaluated using multiple statistical methods. RESULTS: Principal components analyses did not reveal gene-level associations between GC or CASR and colorectal neoplasia; however, a significant gene-level association between GC and 25(OH)D concentrations (P < 0.01) was observed. At the individual SNP level and following multiple comparisons adjustments, significant associations were observed between seven GC (rs7041, rs222035, rs842999, rs1155563, rs12512631, rs16846876, and rs1746825) polymorphisms and circulating measures of 25(OH)D (adjusted P < 0.01) and CASR SNP rs1042636 and proximal colorectal neoplasia (adjusted P = 0.01). CONCLUSIONS: These results show a possible association between variation in CASR and odds of colorectal neoplasia as well as the potential role of variation in GC with circulating 25(OH)D concentrations. IMPACT: Additional research is warranted to determine the mechanism of GC genotype in influencing 25(OH)D concentrations and to further elucidate the role of CASR in colorectal neoplasia.
Language: English
Topic: Vitamin D Research Studies
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: National Cancer Institute
Awards: VDR Variants, Nutrient Intakes, and Adenoma Recurrence, G2159449340, G2159721025, G4040726804, Cancer Prevention and Control Translational Research, G5522739376, Vitamin D Status, Genetic Variation in Vitamin D Signaling and Metabolism, and Ri, G714331257, Colon Cancer Prevention Program Project Grant, Specialized Program Research Excellence (SPORE) in Gastrointestinal Cancer, University of Arizona Cancer Center - Cancer Center Support Grant
OpenAlex ID: W2139745438