Vitamin D receptor gene polymorphisms, bioavailable 25-hydroxyvitamin D, and hepatocellular carcinoma survival

• Published in: JNCI : Journal of the National Cancer Institute 2024-10, Vol.116 (10), p.1687-1696
• Main Authors: Shu, Jing, Zhang, Mingjie, Dong, Xiaocong, Long, Jingan, Li, Yunshan, Tan, Peishan, He, Tongtong, Giovannucci, Edward L, Zhang, Xuehong, Zhou, Zhongguo, Xu, Yanjun, Xu, Xiaojun, Peng, Tianyou, Lu, Jialin, Chen, Minshan, Zhu, Huilian, Zhang, Yaojun, Fang, Aiping
• Format: Article
• Language: English
• ISSN: 0027-8874; 1460-2105; 1460-2105
• DOI: 10.1093/jnci/djae116

Little is known about the role of vitamin D receptor polymorphisms and their interaction with vitamin D status in hepatocellular carcinoma (HCC) prognosis. We evaluated the association of TaqI, BsmI, Cdx-2, and ApaI polymorphisms, individually and in combination, with liver cancer-specific (LCSS) and overall survival (OS) among 967 patients with newly diagnosed HCC. Subsequently, we examined whether these polymorphisms modified the association between serum bioavailable 25-hydroxyvitamin D (25OHD) concentrations and survival. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 1017 days, 393 deaths occurred, with 360 attributed to HCC. Having TaqI G allele (HRper allele = 1.30, 95% CI = 1.08 to 1.57) or BsmI T allele (HRper allele = 1.41, 95% CI = 1.01 to 1.99) was associated with worse LCSS. Carrying increasing numbers of protective alleles was associated with superior LCSS (HR6-8 vs 0-3 = 0.52, 95% CI = 0.34 to 0.80). The inverse association of bioavailable 25OHD with LCSS was only significant in patients with TaqI AA (HRQuartile 4 vs Quartile 1 = 0.63, 95% CI = 0.44 to 0.92), BsmI CC (HRQuartile 4 vs Quartile 1 = 0.62, 95% CI = 0.44 to 0.88), and 6 to 8 protective alleles (HRQuartile 4 vs Quartile 1 = 0.45, 95% CI = 0.23 to 0.87). Similar associations were observed for OS. Patients carrying wild-type TaqI, BsmI, or more protective alleles had improved survival and might benefit from optimizing bioavailable 25OHD status.