Meta-Analysis
Copyright ©The Author(s) 2023.
World J Gastrointest Oncol. Dec 15, 2023; 15(12): 2225-2236
Published online Dec 15, 2023. doi: 10.4251/wjgo.v15.i12.2225
Table 1 Systematic review of MBOAT7 rs641738 and hepatocellular carcinoma susceptibility
Ref.
Country
Cohort characteristics
Study design
Genotyping method
Genetic model(s)
Main results
Conclusion
Thabet et al[8], 2016Multi-countriesHCV-related HCC1706 with chronic HCV infection, divided into two cohorts: Discovery cohort (n = 931) and validation cohort (n = 775)TaqManDominant modelNo significant association was observed with HCC (OR: 0.96; 95%CI: 0.58-1.57)The role of rs641738 is limited to the early stages of liver disease, but not to further progression or occurrence of HCC
Donati et al[9], 2017Multi-countriesNAFLD, HCV, and alcohol-related HCCItalian (n = 765) and United Kingdom (n = 358) NAFLD patients; combined cohort of chronic hepatitis C (n = 597) or alcoholic liver disease (n = 524)TaqManAdditive modelsIn Italian NAFLD patients, the T allele was associated with NAFLD-HCC (OR: 1.65, 95%CI: 1.08-2.55; n = 765). In United Kingdom & Italian NAFLD cohort with non-cirrhotic NAFLD, the T allele remained associated with HCC (OR: 2.10, 95%CI: 1.33-3.31; n = 913). In combined cohort of chronic hepatitis C or alcoholic liver disease, the T allele was independently associated with HCC risk (OR: 1.93, 95%CI: 1.07-3.58; n = 1121)The MBOAT7 rs641738 T allele may predispose to HCC in patients without cirrhosis
Stickel et al[11], 2018Multi-countriesAlcohol-related cirrhotic HCC751 cases with alcohol-related cirrhosis and HCC and 1165 controls with alcohol-related cirrhosis without HCCTaqManAdditive modelsThe risk associated with carriage of MBOAT7 rs641738 was not significant (OR: 1.04, 95%CI: 0.88-1.24)Neither heterozygous nor homozygous carriage of the MBOAT7 rs641738 T allele was associated with HCC risk
Raksayot et al[14], 2019ThailandHBV, HCV, and NBNC-related HCCHealthy controls (n = 105), HBV-related HCC (n = 270), HCV-related HCC (n = 131), and NBNC-related HCC (n = 129)TaqManNAThe genotype distribution and T allele frequencies of MBOAT7 rs641738 were similar between groups (NBNC-HCC vs NBNC-cirrhosis OR: 0.86, 95%CI: 0.51-1.46)The data did not reveal any association between MBOAT7 rs641738 and the development of NBNC-HCC
Wang et al[16], 2021ChinaUnspecified779 HCC cases and 1412 cancer-free controls (controls consist of 678 persistent HBV carriers and 734 spontaneously recovered subjects)MassARRAYDominant, additive, recessive, and allelic modelsThe results suggested no association between MBOAT7-TMC4 rs641738 and HCC risk in most genetic modelsThe work highlights that MBOAT7-TMC4 rs641738 is not associated with the risk of HCC
Bianco et al[12], 2021Multi-countriesNAFLD-related HCCAt-risk individuals (NAFLD cohort, n = 2566 and a replication cohort of 427 German patients with NAFLD). The general population (UKBB cohort, n = 364048). TaqMan & United Kingdom BiLEVE and UKBB Axiom arrayNAIn NAFLD cohort, OR: 1.0, 95%CI: 0.7-1.5; in overall UKBB, OR: 1.3, 95%CI: 0.9-1.8; in non-viral UKBB, OR: 1.3, 95%CI 0.9-1.9Variants in PNPLA3-TM6SF2-GCKR-MBOAT7 were combined in a hepatic fat PRS and PRS predicted HCC more robustly than single variants
Liu et al[13], 2022United KingdomMAFLD-related HCC160979 participants were diagnosed as having MAFLDUnited Kingdom BiLEVE and UKBB Axiom arrayNAModel 2: Adjusted for gender, age, assessment center, genotyping chip, smoking status, physical activity level, overall health rating, average household income, and alcohol consumption. CT vs CC: OR: 1.16, 95%CI: 0.84-1.62; TT vs CC: OR: 1.36, 95%CI: 0.95-1.95MAFLD is independently associated with an increased risk of both intrahepatic and extrahepatic events. The impact of MAFLD on hepatic health events was amplified by variants in fatty liver disease related genes, among which the genetic variations in PNPLA3, TM6SF2, and MBOAT7 play prominent roles
Nahon et al[15], 2023FrenchCompensated cirrhosis (HCV or alcohol)-related HCCCohort 1 (n = 659): Compensated cirrhosis with HCV sustained virologic response. Cohort 2 (n = 486): Compensated alcohol-related cirrhosisTaqManNAIn HCV-cured cohort, CT/TT vs CC: Subhazard ratio: 1.43, 95%CI: 0.68-3.01; In alcohol cohort, CT/TT vs CC: Subhazard ratio: 1.83, 95%CI: 0.85-3.94 (Fine-Gray regression modelling)A 7-SNP genetic risk score was established, which contains PNPLA3, TM6SF2, HSD17B13, APOE, MBOAT7, and WNT3A-WNT9A variants