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

Author:

Shu Jing1ORCID,Zhang Mingjie1,Dong Xiaocong1,Long Jingan12,Li Yunshan1,Tan Peishan1,He Tongtong1ORCID,Giovannucci Edward L34,Zhang Xuehong56ORCID,Zhou Zhongguo7,Xu Yanjun8,Xu Xiaojun8,Peng Tianyou1,Lu Jialin1,Chen Minshan7,Zhu Huilian1,Zhang Yaojun7,Fang Aiping1ORCID

Affiliation:

1. Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, School of Public Health, Sun Yat-sen University , Guangzhou, China

2. Department of Public Health, Guiyang Center for Disease Control and Prevention , Guiyang, China

3. Department of Nutrition, Harvard T.H. Chan School of Public Health , Boston, MA, USA

4. Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, MA, USA

5. Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School , Boston, MA, USA

6. Yale University School of Nursing , Orange, CT, USA

7. Department of Hepatobiliary Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center , Guangzhou, China

8. Department of Chronic Noncommunicable Disease Prevention and Control, Guangdong Provincial Center for Disease Control and Prevention , Guangzhou, China

Abstract

Abstract Background Little is known about the role of vitamin D receptor polymorphisms and their interaction with vitamin D status in hepatocellular carcinoma (HCC) prognosis. Methods 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). Results 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 statistically significant only 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. Conclusions Patients carrying wild-type TaqI, BsmI, or more protective alleles had improved survival and might benefit from optimizing bioavailable 25OHD status.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Guangdong Province

Science and Technology Program of Guangzhou

Publisher

Oxford University Press (OUP)

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