Association of circulating 25-Hydroxyvitamin D and its related genetic variations with hepatocellular carcinoma incidence and survival

BACKGROUND: Vitamin D plays a key role of anti-cancer process, however, the association of vitamin D level and its related genetic variants with hepatocellular carcinoma (HCC) risk and prognosis is not fully understood. METHODS: We enrolled 100 HCC patients and 8,242 health controls from Sir Run Run Shaw Hospital. Logistic regression model was used to calculate the odds ratio (OR) and 95% CI for HCC risk according to serum 25(OH)D concentration. Mendelian randomization (MR) approach was also conducted to validate the potential causal association of 25(OH)D with HCC risk. Hazard ratio (HR) for the association of SNPs with overall survival and disease-free survival was assessed by multivariate Cox hazard proportional regression model. RESULTS: Plasma 25(OH)D level greater than 20 ng/mL increased HCC risk (OR =7.56, 95% CI: 4.58–12.50). MR analysis also showed a slightly increased risk of HCC by 25(OH)D increasing, yet did not reach statistical significance (OR =1.03, 95% CI: 0.31–3.47). With regard to HCC survival, compared to patients with rs8018720 GG genotype, patients with rs8018720 CC/CG genotype had a longer disease-free survival time (HR =0.39, 95% CI: 0.18–0.81). There was an interaction between rs12785878 and 25(OH)D level in continuous scale for HCC mortality. An interaction between rs12785878 and dichotomized 25(OH)D concentration for disease-free survival of HCC patients was also confirmed. CONCLUSIONS: There is hazard of circulating 25(OH)D concentration for HCC occurrence, but protective effect of the interaction between circulating 25(OH)D concentration and its related genetic variation for HCC prognosis. Further study is needed to confirm or refute these findings in a larger population.