Center for Precision Medicine and Epigenome Research Center, China Medical University Hospital, Taichung 40447, Taiwan.
Million-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan.
Int J Mol Sci. 2023 Nov 16;24(22):16417. doi: 10.3390/ijms242216417.
Liver cancer is caused by complex interactions among genetic factors, viral infection, alcohol abuse, and metabolic diseases. We conducted a genome-wide association study and polygenic risk score (PRS) model in Taiwan, employing a nonspecific etiology approach, to identify genetic risk factors for hepatocellular carcinoma (HCC). Our analysis of 2836 HCC cases and 134,549 controls revealed 13 novel associated loci such as the gene, noncoding genes, liver-fibrosis-related genes, metabolism-related genes, and HCC-related pathway genes. We incorporated the results from the UK Biobank and Japanese database into our study for meta-analysis to validate our findings. We also identified specific subtypes of the major histocompatibility complex that influence both viral infection and HCC progression. Using this data, we developed a PRS to predict HCC risk in the general population, patients with HCC, and HCC-affected families. The PRS demonstrated higher risk scores in families with multiple HCCs and other cancer cases. This study presents a novel approach to HCC risk analysis, identifies seven new genes associated with HCC development, and introduces a reproducible PRS model for risk assessment.
肝癌是由遗传因素、病毒感染、酗酒和代谢性疾病等多种因素复杂相互作用引起的。我们采用非特异性病因学方法，在台湾进行了全基因组关联研究和多基因风险评分（PRS）模型，以确定肝细胞癌（HCC）的遗传风险因素。我们对 2836 例 HCC 病例和 134549 例对照进行了分析，发现了 13 个新的相关位点，如基因、非编码基因、肝纤维化相关基因、代谢相关基因和 HCC 相关途径基因。我们将来自英国生物银行和日本数据库的结果纳入我们的研究进行荟萃分析，以验证我们的发现。我们还确定了主要组织相容性复合体的特定亚型，这些亚型既影响病毒感染，也影响 HCC 的进展。我们利用这些数据开发了一种 PRS 来预测一般人群、HCC 患者和 HCC 相关家族的 HCC 风险。PRS 在有多个 HCC 和其他癌症病例的家族中显示出更高的风险评分。本研究提出了一种 HCC 风险分析的新方法，确定了 7 个与 HCC 发展相关的新基因，并引入了一种可重复的 PRS 模型进行风险评估。
