Associations between modifiable risk factors and hepatocellular carcinoma: a trans-ancestry Mendelian randomization study

作者：Xiaoxia Wei, Chenglei Yang, Qiuling Lin, Moqin Qiu, Qiuping Wen, Zihan Zhou, Yanji Jiang, Peiqin Chen, Xiumei Liang, Ji Cao, Juan Tang, Yuying Wei, Hongping Yu, Yingchun Liu · 发表于：BMC Cancer · 年份：2024 · DOI：10.1186/s12885-024-12525-x · 被引用次数：11 · 研究领域：Genetic Associations and Epidemiology、Liver Disease Diagnosis and Treatment、Folate and B Vitamins Research

BACKGROUND: Potentially modifiable risk factors for hepatocellular carcinoma (HCC) have been investigated in observational epidemiology studies in East Asian and European populations, whereas the causal associations of most of these risk factors remain unclear. METHODS: We collected genome-wide association summary statistics of 22 modifiable risk factors in East Asians and 33 risk factors in Europeans. Genetic summary statistics of HCC were sourced from the Biobank Japan study (1,866 cases and 195,745 controls) for East Asians, and the deCODE genetics study (406 cases and 49,302 controls) and the UK Biobank (168 cases and 372 016 controls) for Europeans. Two-sample Mendelian randomization (MR) analyses were performed independently for East Asian and European populations. RESULTS: In East Asians, genetically predicted alcohol frequency, ever drinkers, aspartate aminotransferase (AST), hypothyroidism, chronic hepatitis B, and chronic hepatitis C, metabolic dysfunction-associated steatotic liver disease (MASLD), and autoimmune hepatitis were significantly associated with an increased HCC risk (P < 0.05/22). Among European population, alanine transaminase, AST, MASLD, percent liver fat, and liver iron content were significantly associated with a higher risk of HCC (P < 0.05/33). The replication dataset and meta-analysis further confirmed these results. CONCLUSIONS: Although East Asian and European populations have different factors for HCC, their common modifiable risk factors AS...