血清一碳代谢物水平与肝细胞癌风险的关系。
Prediagnostic levels of serum one-carbon metabolites and risk of hepatocellular carcinoma.
机构信息
Authors' Affiliations: Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute; and Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania; Institute of Metabolic Disease, Baylor Research Institute, Dallas, Texas; Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; and Department of Epidemiology, Shanghai Cancer Institute, Shanghai, PR China.
出版信息
Cancer Epidemiol Biomarkers Prev. 2013 Oct;22(10):1884-93. doi: 10.1158/1055-9965.EPI-13-0497. Epub 2013 Jul 29.
BACKGROUND
Rats fed diets deficient in choline develop hepatocellular carcinoma. Tumor DNA from these animals is characteristically hypomethylated, suggesting that disruption of the one-carbon metabolism pathway is an underlying mechanism for hepatocarcinogenesis. Prospective studies in humans on circulating choline and other one-carbon metabolites and hepatocellular carcinoma risk have been lacking.
METHODS
We prospectively examined the association between prediagnostic serum concentrations of one-carbon metabolites including betaine, choline, cystathionine, homocysteine, methionine, 5-methyltetrahydrofolate (5-MTHF), pyridoxal-5-phosphate (PLP, the bioactive form of vitamin B6) and S-adenosylmethionine (SAM), and risk of developing hepatocellular carcinoma based on a nested case-control study of 297 incident cases and 631 matched controls from a cohort of 18,244 men in Shanghai, China. Logistic regression methods were used to calculate ORs and 95% confidence intervals (CI) adjusted for established risk factors for hepatocellular carcinoma.
RESULTS
Serum choline and PLP were associated with statistically significant reduced risk of hepatocellular carcinoma, whereas serum cystathionine, methionine, and SAM were associated with increased hepatocellular carcinoma risk (all Ptrend < 0.05). The inverse associations for hepatocellular carcinoma risk with choline and PLP remained statistically significant after adjusting for all potential confounders. The multivariate-adjusted ORs (95% CIs) for the highest versus lowest quintiles of serum choline and PLP were 0.35 (0.16-0.78; P = 0.010) and 0.44 (0.25-0.78; P = 0.005), respectively. There were no associations for hepatocellular carcinoma risk with 5-MTHF, betaine, or homocysteine.
CONCLUSION
The inverse associations between choline and vitamin B6 and the risk of hepatocellular carcinoma development are novel and warrant further investigation.
IMPACT
Identifying new modifiable factors for hepatocellular carcinoma prevention is warranted.
背景
食用胆碱缺乏的饮食会导致大鼠患上肝癌。这些动物的肿瘤 DNA 特征性地低甲基化，表明一碳代谢途径的破坏是肝癌发生的潜在机制。在人类中，关于循环胆碱和其他一碳代谢物与肝细胞癌风险的前瞻性研究一直缺乏。
方法
我们前瞻性地研究了包括甜菜碱、胆碱、胱硫醚、同型半胱氨酸、蛋氨酸、5-甲基四氢叶酸（5-MTHF，维生素 B6 的生物活性形式）和 S-腺苷甲硫氨酸（SAM）在内的一碳代谢物在诊断前血清浓度与肝细胞癌风险之间的关联，该研究基于中国上海一个队列的 18244 名男性中的一个巢式病例对照研究，共纳入 297 例肝癌新发病例和 631 例匹配对照。使用逻辑回归方法计算 OR 和 95%置信区间（CI），并对肝癌的既定危险因素进行调整。
结果
血清胆碱和 PLP 与肝癌风险呈显著降低相关，而血清胱硫醚、蛋氨酸和 SAM 与肝癌风险增加相关（所有 Ptrend<0.05）。调整所有潜在混杂因素后，胆碱和 PLP 与肝癌风险呈负相关仍然具有统计学意义。血清胆碱和 PLP 最高五分位与最低五分位相比，多变量调整后的 OR（95%CI）分别为 0.35（0.16-0.78；P=0.010）和 0.44（0.25-0.78；P=0.005）。5-MTHF、甜菜碱或同型半胱氨酸与肝癌风险无关联。
结论
胆碱和维生素 B6 与肝细胞癌发展风险之间的负相关关系是新颖的，值得进一步研究。
意义
确定肝细胞癌预防的新的可改变因素是必要的。
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