Service d'Hépatologie, Hôpital Jean Verdier, AP-HP, Bondy, and Université Paris 13/UFR SMBH, Bobigny, France.
J Hepatol. 2012 Sep;57(3):663-74. doi: 10.1016/j.jhep.2012.02.035. Epub 2012 May 16.
Liver carcinogenesis is a complex and multi-factorial process, in which both environmental and genetic features interfere and contribute to malignant transformation. Patients with cirrhosis are particularly exposed and justify periodical screenings in order to detect the early development of hepatocellular carcinoma (HCC). The risk of HCC is, however, not identical from one patient to another. The identification of host factors that may also play an important role in HCC development may improve our understanding of the implications of the various biological pathways involved in liver carcinogenesis; such progress may as well help refine the selection of patients who could benefit from specific preventative measures or could be given adapted screening policies. Numerous candidate-gene studies have reported associations between single nucleotide polymorphisms (SNPs) and the presence of HCC. Some of these publications unfortunately suffer from major methodological drawbacks because of their case-control, retrospective and monocentric aspect. Prospective cohort studies conducted in large homogeneous populations and comprising a sufficient number of events during follow-up may overcome these pitfalls, but require a long time to be conducted and are still scarce. More recently, the first Genome Wide Association studies (GWAs) have enabled the identification of unsuspected loci that may be involved in various steps implicated in liver tumourigenesis. Taken together, these studies highlight variants that modulate oxidative stress, iron metabolism, inflammatory and immune responses, DNA repair mechanisms or systems involved in cell-cycle regulation as genetic traits susceptible to modify the natural history of cirrhotic patients and partly explain the observed differences in the risk of HCC occurrence. However, large genetic epidemiology studies in the field of cancer diseases have suggested the limited ability of polymorphic traits, alone, to refine individual prognosis. The integration of various panels of genes into clinical scores may in the near future define a "genomic risk prediction" specific to liver cancer developed in cirrhotic patients.
肝癌的发生是一个复杂的多因素过程，其中环境和遗传因素相互干扰并促成恶性转化。肝硬化患者尤其容易受到影响，需要定期进行筛查，以检测肝癌（HCC）的早期发生。然而，每个患者的 HCC 风险并不相同。确定宿主因素可能在 HCC 发展中也发挥重要作用，这可能有助于我们更好地理解涉及肝癌发生的各种生物学途径的意义；这种进展还有助于完善选择可能受益于特定预防措施或可以给予适应性筛查政策的患者。许多候选基因研究报告了单核苷酸多态性（SNPs）与 HCC 存在之间的关联。其中一些出版物由于其病例对照、回顾性和单中心性质存在严重的方法学缺陷。在大型同质人群中进行的前瞻性队列研究，并在随访期间包含足够数量的事件，可能会克服这些缺陷，但需要很长时间才能进行，而且仍然很少。最近，第一项全基因组关联研究（GWAs）已经确定了可能涉及肝癌发生中各种步骤的未被发现的基因座。总的来说，这些研究强调了调节氧化应激、铁代谢、炎症和免疫反应、DNA 修复机制或细胞周期调节系统的变异体作为遗传特征，可能改变肝硬化患者的自然病程，并部分解释了 HCC 发生风险的观察到的差异。然而，癌症领域的大型遗传流行病学研究表明，多态性特征本身单独预测个体预后的能力有限。将各种基因组合成临床评分可能在不久的将来定义特定于肝硬化患者肝癌的“基因组风险预测”。
