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POLYMORPHIC VARIATION IN THE GC AND CASR GENES AND ASSOCIATIONS WITH VITAMIN D METABOLITE CONCENTRATION AND METACHRONOUS COLORECTAL NEOPLASIA
- Publication Year :
- 2011
-
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. Cancer Epidemiol Biomarkers Prev; 21(2); 368–75. ©2011 AACR.
- Subjects :
- Vitamin
Dietary Fiber
Male
medicine.medical_specialty
Genotype
Epidemiology
Vitamin D-binding protein
Metabolite
Single-nucleotide polymorphism
Biology
Polymorphism, Single Nucleotide
Article
chemistry.chemical_compound
Double-Blind Method
Risk Factors
Internal medicine
Genetic variation
medicine
Vitamin D and neurology
SNP
Humans
Genetic Predisposition to Disease
Vitamin D
Aged
Randomized Controlled Trials as Topic
Vitamin D-Binding Protein
Ursodeoxycholic Acid
Genetic Variation
Neoplasms, Second Primary
Middle Aged
Endocrinology
Treatment Outcome
Oncology
chemistry
Clinical Trials, Phase III as Topic
Female
Colorectal Neoplasms
Receptors, Calcium-Sensing
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....a2598eb3b1337e390abc7ff2e26720c5