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肝癌的发生是一个多阶段、多因素长期暴露和累积的复杂过程。而肝硬化则被认为是肝癌的一种癌前状态,因此,应该对肝硬化患者进行定期的监测,以及早发现肝癌的发生。然而,肝硬化患者之间发生肝癌的风险却各不相同,对肝癌发生中遗传学因素作用的确认有利于人们探究各种参与肝癌发生的生物学途径,并可帮助确认哪些患者可以从针对性的预防和监控措施中获益。大量的候选基因关联研究已经报道了作为第三代遗传标记的单核苷酸多态性与肝癌发生的关系,但其中一部分回顾性病例对照研究却存在方法学问题。大样本的多变量前瞻性研究虽然克服了以上缺点,但实施起来比较复杂,且需要一个较长的时期,报道数量也相对较少。全基因组关联研究能够确认之前未被怀疑的,参与肝癌发生多个阶段的位点,但也存在一定的方法学偏倚。本文就以上这些研究关于单核苷酸多态性参与调控肝硬化患者肝癌发生机制的研究现状做一综述。
The occurrence of liver cancer is a complex and multi-stage long-term exposure and accumulation process. Cirrhosis is considered a precancerous condition of liver cancer. Therefore, regular monitoring should be performed on patients with cirrhosis and early detection of liver cancer. However, the risk of developing liver cancer varies among patients with cirrhosis, and confirmation of the role of genetic factors in the development of hepatocellular carcinoma facilitates the exploration of various biological pathways involved in the development of hepatocellular carcinoma and helps identify which patients can be targeted Benefit from prevention and control measures. A large number of candidate gene association studies have reported the association of single nucleotide polymorphisms as third generation genetic markers with the development of hepatocellular carcinoma. However, some retrospective case-control studies have methodological issues. Although the multivariable prospective study of the large sample overcomes the above shortcomings, it is more complicated to implement and requires a longer period of time with a relatively small number of reports. Genome-wide association studies have identified previously undisclosed sites that are involved in multiple stages of hepatocellular carcinoma, but also have some methodological bias. This review summarizes the current status of these studies on the mechanism of single nucleotide polymorphisms involved in the regulation of liver cancer in patients with cirrhosis.