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||Genetic predictors of circulating 25-hydroxyvitamin D and prognosis after colorectal cancer.
||Neumeyer S, Butterbach K, Banbury BL, Berndt SI, Campbell PT, Chlebowski RT, Chan AT, Giovannucci EL, Joshi AD, Ogino S, Song M, McCullough ML, Maalmi H, Manson JE, Sakoda LC, Schoen RE, Slattery ML, White E, Win AK, Figueiredo JC, Hopper JL, Macrae FA, Peters U, Brenner H, Hoffmeister M, Newcomb PA, Chang-Claude J
||Cancer Epidemiol Biomarkers Prev
||2020 Mar 18
||BACKGROUND: Low serum 25-hydroxyvitamin D (25(OH)D) concentrations in colorectal cancer (CRC) patients have been consistently associated with higher mortality in observational studies. It is unclear whether low 25(OH)D levels directly influence CRC mortality. To minimize bias, we use genetic variants associated with vitamin D levels to evaluate the association with overall and CRC-specific survival. METHODS: Six genetic variants have been robustly identified to be associated with 25(OH)D levels in genome-wide association studies. Based on data from the International Survival Analysis in Colorectal Cancer Consortium (ISACC) the individual genetic variants and a weighted genetic risk score were tested for association with overall and CRC-specific survival using Cox proportional hazards models in 7 657 stage I-IV CRC patients of which 2 438 died from any cause and 1 648 died from CRC. RESULTS: The 25(OH)D decreasing allele of single nucleotide polymorphism (SNP) rs2282679 (GC) was associated with poorer CRC-specific survival, although not significant after multiple-testing correction. None of the other five SNPs showed an association. The genetic risk score showed non-significant associations with increased overall (HR=1.54, 95% CI:0.86-2.78) and CRC-specific mortality (HR=1.76, 95% CI:0.86-3.58). A significant increased risk of overall mortality was observed in women (HR=3.26, 95% CI:1.45-7.33, p-value for heterogeneity=0.01) and normal-weight individuals (HR=4.14, 95% CI:1.50-11.43, p-value for heterogeneity=0.02). CONCLUSIONS: Our results provided little evidence for an association of genetic predisposition of lower vitamin D levels with increased overall or CRC-specific survival, although power might have been an issue. IMPACT: Further studies are warranted to investigate the association in specific subgroups.