Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, California.
Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.
Liver Int. 2019 Aug;39(8):1490-1503. doi: 10.1111/liv.14182. Epub 2019 Jul 10.
BACKGROUND & AIMS: The potential interaction between family history of liver cancer and HBV infection on liver cancer has not been fully examined.
We conducted a population-based case-control study composed of 2011 liver cancer cases and 7933 controls in Jiangsu province, China from 2003 to 2010. Data on major risk or protective factors were collected and HBV/HCV sero-markers were assayed using blood samples. Semi-Bayes (SB) adjustments were applied to provide posterior estimates.
Both family history of liver cancer (adjusted odds ratios [OR]: 4.32, 95% confidence intervals [CI]: 3.25-5.73) and hepatitis B surface antigen (HBsAg) positivity (adjusted OR: 9.94, 95% CI: 8.33-11.87) were strongly associated with liver cancer development. For individuals with different combinations of serological markers, the adjusted ORs were 8.45 (95% CI: 5.16-13.82) for HBsAg- and HBcAb-positive; 7.57 (95% CI: 4.87-11.77) for HBsAg-, HBeAg- and HBcAb-positive; and 3.62 (95% CI: 2.47-5.31) for HBsAg-, HBeAb- and HBcAb-positive, compared to all negatives in HBV serological markers. One log increase in HBV DNA level was associated with 17% increased risk (adjusted OR: 1.17, 95% CI: 1.03-1.32). The SB-adjusted OR of HBV-positive individuals with family history of liver cancer was 41.34 (95% posterior interval [PI]: 23.69-72.12) compared with those HBV-negative without family history. Relative excess risk due to additive interaction, the attributable proportion and synergy index were 73.13, 0.87 and 8.04 respectively. Adjusted ratio of OR for multiplicative interaction was 2.84 (95% CI: 1.41-5.75).
Super-additive and super-multiplicative interactions may exist between family history of liver cancer and HBV infection on the development of liver cancer.
家族肝癌史与乙型肝炎病毒（HBV）感染在肝癌发病中的相互作用尚未完全阐明。
我们在中国江苏省进行了一项基于人群的病例对照研究，纳入了 2003 年至 2010 年的 2011 例肝癌病例和 7933 例对照。收集了主要危险因素或保护因素的数据，并使用血样检测 HBV/HCV 血清标志物。采用半贝叶斯（SB）调整方法提供后验估计。
家族肝癌史（调整后的比值比 [OR]：4.32，95%置信区间 [CI]：3.25-5.73）和乙肝表面抗原（HBsAg）阳性（调整后的 OR：9.94，95%CI：8.33-11.87）均与肝癌的发生密切相关。对于不同血清学标志物组合的个体，HBsAg 和 HBcAb 阳性者的调整比值比为 8.45（95%CI：5.16-13.82）；HBsAg、HBeAg 和 HBcAb 阳性者为 7.57（95%CI：4.87-11.77）；HBsAg、HBeAb 和 HBcAb 阳性者为 3.62（95%CI：2.47-5.31），而 HBV 血清标志物均为阴性。HBV DNA 水平每增加一个对数，肝癌发病风险增加 17%（调整后的 OR：1.17，95%CI：1.03-1.32）。与 HBV 阴性且无家族肝癌史者相比，HBV 阳性且有家族肝癌史者的 SB 调整后 OR 为 41.34（95%后验区间 [PI]：23.69-72.12）。加性交互作用的相对超额风险、归因比例和协同指数分别为 73.13、0.87 和 8.04。乘法交互作用的调整比值比为 2.84（95%CI：1.41-5.75）。
家族肝癌史和 HBV 感染在肝癌发病中可能存在超相加和超相乘作用。
