Joint effects of colorectal cancer susceptibility loci, circulating 25-hydroxyvitamin D and risk of colorectal cancer - PubMed (original) (raw)

Joint effects of colorectal cancer susceptibility loci, circulating 25-hydroxyvitamin D and risk of colorectal cancer

Linda T Hiraki et al. PLoS One. 2014.

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. GRS-31 and CRC stratified by quartiles of 25(OH)D.

Demonstrated no evidence for variation in CRC risk estimates associated with GRS-31, stratified across quartiles of 25(OH)D (phet = 0.98).

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