Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta GA, USA.
Hepatology. 2014 Oct;60(4):1222-30. doi: 10.1002/hep.27079. Epub 2014 Aug 28.
The association between vitamin D status and hepatocellular carcinoma (HCC) has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology. Our objective was to investigate the association between prediagnostic circulating 25-hydroxyvitamin D [25(OH)D] serum levels and the risk of HCC in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n = 138) diagnosed between 1992 and 2010 was matched to one control by age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRRs) of HCC associated with continuous (per 10 nmol/L) or categorical levels (tertiles or a priori-defined categories) of prediagnostic 25(OH)D were calculated using conditional logistic regression. Higher 25(OH)D levels were associated with a 49% reduction in the risk of HCC (highest versus lowest tertile: multivariable IRR = 0.51, 95% confidence interval [CI], 0.26 to 0.99; Ptrend = 0.04; per 10 nmol/L increase: IRR = 0.80, 95% CI, 0.68-0.94). The finding did not vary substantially by time from enrolment to diagnosis, and did not change after adjustment for biomarkers of preexisting liver damage, nor chronic infection with hepatitis B or C viruses. The findings were not modified by body size or smoking status.
In this prospective study on western European populations, serum levels of 25(OH)D were inversely associated with the risk of HCC. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest surrounding the potentially cancer-protective roles of vitamin D, additional studies in different populations are required.
尽管有实验证据表明维生素 D 在肝脏病理生理学中起着重要作用，但维生素 D 状态与肝细胞癌 (HCC) 之间的关系尚未得到充分研究。我们旨在通过欧洲前瞻性癌症与营养研究（EPIC）队列中 52 万名参与者的前瞻性嵌套病例对照研究，调查诊断前循环 25-羟维生素 D [25(OH)D] 血清水平与 HCC 风险之间的关系。每个病例（n=138）均于 1992 年至 2010 年间诊断，并按年龄、性别、研究中心、采血日期和时间以及禁食状态与 1 名对照相匹配。通过液相色谱/串联质谱法测量血清基线 25(OH)D 水平。使用条件逻辑回归计算 HCC 相关的多变量发生率比（IRR）与连续（每 10 nmol/L）或分类水平（三分位数或预先定义的类别）的诊断前 25(OH)D 之间的关系。较高的 25(OH)D 水平与 HCC 风险降低 49%相关（最高与最低三分位：多变量 IRR=0.51，95%置信区间 [CI]，0.26 至 0.99；Ptrend=0.04；每增加 10 nmol/L：IRR=0.80，95%CI，0.68-0.94）。该发现与从入组到诊断的时间间隔没有明显差异，并且在调整了预先存在的肝损伤生物标志物、乙型或丙型肝炎病毒慢性感染后也没有改变。体重指数或吸烟状况并未改变结果。
在这项针对西欧人群的前瞻性研究中，血清 25(OH)D 水平与 HCC 风险呈负相关。鉴于这种癌症在低风险发达国家的发病率不断上升，以及维生素 D 具有潜在的抗癌作用，引起了强烈的公共卫生关注，因此需要在不同人群中开展更多的研究。
