dc.contributor.author | Hiraki, Linda T. | en_US |
dc.contributor.author | Joshi, Amit D. | en_US |
dc.contributor.author | Ng, Kimmie | en_US |
dc.contributor.author | Fuchs, Charles S. | en_US |
dc.contributor.author | Ma, Jing | en_US |
dc.contributor.author | Hazra, Aditi | en_US |
dc.contributor.author | Peters, Ulrike | en_US |
dc.contributor.author | Karlson, Elizabeth W. | en_US |
dc.contributor.author | Giovannucci, Edward | en_US |
dc.contributor.author | Kraft, Peter | en_US |
dc.contributor.author | Chan, Andrew T. | en_US |
dc.date.accessioned | 2014-04-11T14:11:06Z | |
dc.date.issued | 2014 | en_US |
dc.identifier.citation | Hiraki, L. T., A. D. Joshi, K. Ng, C. S. Fuchs, J. Ma, A. Hazra, U. Peters, et al. 2014. “Joint Effects of Colorectal Cancer Susceptibility Loci, Circulating 25-Hydroxyvitamin D and Risk of Colorectal Cancer.” PLoS ONE 9 (3): e92212. doi:10.1371/journal.pone.0092212. http://dx.doi.org/10.1371/journal.pone.0092212. | en |
dc.identifier.issn | 1932-6203 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:12064383 | |
dc.description.abstract | Background: Genome wide association studies (GWAS) have identified several SNPs associated with colorectal cancer (CRC) susceptibility. Vitamin D is also inversely associated with CRC risk. Methods: We examined main and joint effects of previously GWAS identified genetic markers of CRC and plasma 25-hydroxyvitamin D (25(OH)D) on CRC risk in three prospective cohorts: the Nurses' Health Study (NHS), the Health Professionals Follow-up Study (HPFS), and the Physicians' Health Study (PHS). We included 1895 CRC cases and 2806 controls with genomic DNA. We calculated odds ratios and 95% confidence intervals for CRC associated with additive genetic risk scores (GRSs) comprised of all CRC SNPs and subsets of these SNPs based on proximity to regions of increased vitamin D receptor binding to vitamin D response elements (VDREs), based on published ChiP-seq data. Among a subset of subjects with additional prediagnostic 25(OH)D we tested multiplicative interactions between plasma 25(OH)D and GRS's. We used fixed effects models to meta-analyze the three cohorts. Results: The per allele multivariate OR was 1.12 (95% CI, 1.06–1.19) for GRS-proximalVDRE; and 1.10 (95% CI, 1.06–1.14) for GRS-nonproxVDRE. The lowest quartile of plasma 25(OH)D compared with the highest, had a multivariate OR of 0.63 (95% CI, 0.48–0.82) for CRC. We did not observe any significant interactions between any GRSs and plasma 25(OH)D. Conclusions: We did not observe evidence for the modification of genetic susceptibility for CRC according to vitamin D status, or evidence that the effect of common CRC risk alleles differed according to their proximity to putative VDR binding sites. | en |
dc.language.iso | en_US | en |
dc.publisher | Public Library of Science | en |
dc.relation.isversionof | doi:10.1371/journal.pone.0092212 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3966783/pdf/ | en |
dash.license | LAA | en_US |
dc.subject | Biology and Life Sciences | en |
dc.subject | Computational Biology | en |
dc.subject | Evolutionary Biology | en |
dc.subject | Population Genetics | en |
dc.subject | Genetic Polymorphism | en |
dc.subject | Medicine and Health Sciences | en |
dc.subject | Epidemiology | en |
dc.subject | Cancer Epidemiology | en |
dc.subject | Genetic Epidemiology | en |
dc.subject | Gastroenterology and Hepatology | en |
dc.subject | Gastrointestinal Cancers | en |
dc.subject | Oncology | en |
dc.subject | Cancer Risk Factors | en |
dc.subject | Environmental Causes of Cancer | en |
dc.subject | Genetic Causes of Cancer | en |
dc.subject | Nutritional Correlates of Cancer | en |
dc.subject | Cancers and Neoplasms | en |
dc.subject | Gastrointestinal Tumors | en |
dc.title | Joint Effects of Colorectal Cancer Susceptibility Loci, Circulating 25-Hydroxyvitamin D and Risk of Colorectal Cancer | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | PLoS ONE | en |
dash.depositing.author | Joshi, Amit D. | en_US |
dc.date.available | 2014-04-11T14:11:06Z | |
dc.identifier.doi | 10.1371/journal.pone.0092212 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Joshi, Amit | |
dash.contributor.affiliated | Ma, Jing | |
dash.contributor.affiliated | Karlson, Elizabeth | |
dash.contributor.affiliated | Fuchs, Charles | |
dash.contributor.affiliated | Giovannucci, Edward | |
dash.contributor.affiliated | Chan, Andrew | |
dash.contributor.affiliated | Kraft, Phillip | |