PDF(Pubmed)
Abstract：
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 AST and MASLD for HCC, offer valuable insights for targeted intervention strategies to mitigate society burden of HCC.
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 AST and MASLD for HCC, offer valuable insights for targeted intervention strategies to mitigate society burden of HCC.
摘要：
背景：在东亚和欧洲人群的观察性流行病学研究中，已经调查了肝细胞癌（HCC）的潜在可改变的危险因素，而大多数这些危险因素之间的因果关系尚不清楚.
方法：我们收集了东亚人22个可改变的危险因素和欧洲人33个危险因素的全基因组关联汇总统计。HCC的遗传摘要统计来自日本生物银行的东亚人研究（1,866例和195,745例对照）。以及欧洲的deCODE遗传学研究（406例和49,302例对照）和英国生物库（168例和372016例对照）。对东亚和欧洲人群独立进行了两个样本孟德尔随机化（MR）分析。
结果：在东亚人中，基因预测的酒精频率，曾经喝酒，天冬氨酸转氨酶（AST），甲状腺功能减退,慢性乙型肝炎，和慢性丙型肝炎，代谢功能障碍相关的脂肪变性肝病（MASLD），和自身免疫性肝炎与HCC风险增加显著相关(P<0.05/22)。在欧洲人口中，丙氨酸转氨酶，AST,MASLD,肝脏脂肪百分比，和肝脏铁含量与肝癌的高风险显著相关(P<0.05/33)。复制数据集和荟萃分析进一步证实了这些结果。
结论：尽管东亚和欧洲人群有不同的肝癌因素，他们常见的可改变的HCC危险因素AST和MASLD，为有针对性的干预策略提供有价值的见解，以减轻HCC的社会负担。
方法：我们收集了东亚人22个可改变的危险因素和欧洲人33个危险因素的全基因组关联汇总统计。HCC的遗传摘要统计来自日本生物银行的东亚人研究（1,866例和195,745例对照）。以及欧洲的deCODE遗传学研究（406例和49,302例对照）和英国生物库（168例和372016例对照）。对东亚和欧洲人群独立进行了两个样本孟德尔随机化（MR）分析。
结果：在东亚人中，基因预测的酒精频率，曾经喝酒，天冬氨酸转氨酶（AST），甲状腺功能减退,慢性乙型肝炎，和慢性丙型肝炎，代谢功能障碍相关的脂肪变性肝病（MASLD），和自身免疫性肝炎与HCC风险增加显著相关(P<0.05/22)。在欧洲人口中，丙氨酸转氨酶，AST,MASLD,肝脏脂肪百分比，和肝脏铁含量与肝癌的高风险显著相关(P<0.05/33)。复制数据集和荟萃分析进一步证实了这些结果。
结论：尽管东亚和欧洲人群有不同的肝癌因素，他们常见的可改变的HCC危险因素AST和MASLD，为有针对性的干预策略提供有价值的见解，以减轻HCC的社会负担。
