肝癌的家族史与肝细胞癌

　　既往已有很多研究报道在乙型肝炎病毒感染普遍存在的东亚地区中发现了肝癌发病的家族聚集现象。在西方人群中肝癌和肝癌家族史的关系知之甚少。我们在意大利进行了一项病例对照研究，涉及299例HCC患者和431名对照住院患者。根据选定的家族特点，通过二元指标（是或否）及家族史评分（FH score）对家族史数据进行了总结。 根据年龄、性别、研究中心、教育程度、吸烟、饮酒、乙型肝炎表面抗原和/或丙型肝炎抗体阳性等，通过多元逻辑回归模型 获得了比值比（ORs）和相应的95％可信区间（CIs）。我们运用随机效应模型对更新至2011年4月的有肝癌家族史的患者和肝癌患者进行了meta-分析。当使用二元指标（OR，2.38；95%可信区间，1.01-5.58）和FHscore时，对慢性乙型或丙型肝炎病毒感染进行调整后，肝癌家族史与肝癌风险呈现相关性，且连续评分等级的OR值增高。 与无家族史、未患慢性乙肝或丙肝的对照组患者相比，同时暴露与于这些危险因素的实验组患者的OR值为72.48(95% CI, 21.92-239.73)。在meta分析中，在9个病例-对照研究和4个队列研究的基础上，共包含约3,600名肝癌病例，肝癌家族史患者发生肝癌的相对风险是2.50 （95％CI，2.06-3.03）。肝癌家族史可以增加肝细胞癌的发生风险，并且它是独立于肝炎的危险因素。若同时伴有肝癌家族史以及血清中乙型/丙型肝炎病毒标志物阳性，则HCC发生风险可增高70倍以上。
　　

吉林大学第一医院肝胆胰内科 王静云 摘译
本文首次发表于[Hepatology, 2012, 55(5):1416-1425]
 

Family history of liver cancer and hepatocellular carcinoma

Familial clustering of hepatocellular carcinoma (HCC) has been frequently reported in eastern Asiatic countries, where hepatitis B infection is common. Little is known about the relationship between family history of liver cancer and HCC in Western populations. We carried out a case-control study in Italy, involving 229 HCC cases and 431 hospital controls. Data on family history were summarized through a binary indicator (yes/no) and a family history score (FHscore), considering selected family characteristics. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were obtained from unconditional multiple logistic regression models, including terms for age, sex, study center, education, tobacco smoking, alcohol drinking, hepatitis B surface antigen, and/or anti–hepatitis C virus positivity. We also performed a meta-analysis on family history of liver cancer and liver cancer updated to April 2011 using random-effects models. After adjustment for chronic infection with hepatitis B/C viruses, family history of liver cancer was associated with HCC risk, when using both the binary indicator (OR, 2.38; 95% CI, 1.01-5.58) and the FHscore, with increasing ORs for successive score categories. Compared to subjects without family history and no chronic infection with hepatitis B/C viruses, the OR for those exposed to both risk factors was 72.48 (95% CI, 21.92-239.73). In the meta-analysis, based on nine case-control and four cohort studies, for a total of approximately 3,600 liver cancer cases, the pooled relative risk for family history of liver cancer was 2.50 (95% CI, 2.06-3.03). A family history of liver cancer increases HCC risk, independently of hepatitis. The combination of family history of liver cancer and hepatitis B/C serum markers is associated with an over 70-fold elevated HCC risk. 

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