Genetic Association Studies in Hepatocellular Carcinoma: Systematic Meta‐Analyses, a Comprehensive Field Synopsis, and Epidemiological Evidence

ABSTRACT Associations between various genetic variants and the risk of hepatocellular carcinoma (HCC) have been extensively explored but produced contradictory results. The aim of the present systematic meta‐analysis was to determine and validate genetic variants that are associated with HCC risk. Two‐step literature searches of PubMed, Embase, Web of Science, and Google Scholar databases and various meta‐analyses were performed, and a comprehensive field synopsis and epidemiological evidence were provided. A total of 20,081 publications were identified, of which 830 were deemed eligible for inclusion. Eventually, 36 variants in 27 genes were identified to be associated with HCC risk. Moreover, cumulative epidemiological evidence of an association was graded as moderate for nine variants in eight genes ( ESR1 rs2234693, GRP78 rs430397, HLA‐DP rs3077, HLA‐DQ rs2856718, MnSOD rs4880, TNFα rs361525, HFE rs1800562 and rs1799945, and UGT1A7 High/Low) and strong for three variants in three genes ( IL‐1B rs1143627, COL18A1 rs7499, and NQO1 rs1800566); HFE rs1800562 was deemed to have a false‐positive association. Thus, 11 variants in 11 genes were identified to be associated with HCC risk. This synopsis helps elucidate the mechanisms of carcinogenesis of HCC and provides insights into the early diagnosis and novel treatments of HCC by targeting those potential genes.