Prediagnostic Circulating Vitamin D Levels and Risk of Hepatocellular Carcinoma in European Populations: A Nested Case-Control Study
Prediagnostic Circulating Vitamin D Levels and Risk of Hepatocellular Carcinoma in European Populations: A Nested Case-Control Study
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DOI：
10.1002/hep.27079
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发表时间：
2014-10-01
期刊：
影响因子：
13.5
通讯作者：
Jenab, Mazda
中科院分区：
文献类型：
--
作者：
Fedirko, Veronika;Duarte-Salles, Talita;Jenab, Mazda
尽管实验证据支持维生素D在肝脏病理生理学中的重要作用，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。我们的目的是在欧洲癌症与营养前瞻性研究（EPIC）队列的520，000名参与者中进行前瞻性巢式病例对照研究，以调查诊断前循环25-羟基维生素D [25（OH）D]血清水平与HCC风险之间的关系。在1992年至2010年期间诊断的每例病例（n=138）与一个对照组（年龄，性别，研究中心，采血日期和时间以及空腹状态）相匹配。采用液相色谱/串联质谱法测定血清25（OH）D基线水平。使用条件logistic回归计算与诊断前25（OH）D连续（每10 nmol/L）或分类水平（三分位数或优先定义的类别）相关的HCC多变量发病率比（IRR）。较高的25（OH）D水平与HCC风险降低49%相关（最高与最低三分位数：多变量IRR=0.51，95%置信区间[CI]，0.26 - 0.99; P趋势=0.04;每增加10 nmol/L：IRR=0.80，95% CI，0.68-0.94）。从入组到诊断，这一发现没有实质性变化，并且在调整既存肝损伤的生物标志物或慢性B或C型肝炎病毒感染后也没有变化。研究结果并未因体型或吸烟状况而改变。结论：在这项对西欧人群的前瞻性研究中，血清25（OH）D水平与HCC的风险呈负相关。鉴于这种癌症在低风险发达国家的发病率不断上升，以及公众对维生素D潜在的癌症保护作用的强烈兴趣，需要对不同人群进行更多研究。（肝病学2014;60：1222-1230）
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; P-trend=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. Conclusion: 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. (Hepatology 2014;60:1222-1230)