Association of MBOAT7 rs641738 polymorphism with hepatocellular carcinoma susceptibility: A systematic review and meta-analysis

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], 2016	Multi-countries	HCV-related HCC	1706 with chronic HCV infection, divided into two cohorts: Discovery cohort (n = 931) and validation cohort (n = 775)	TaqMan	Dominant model	No 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], 2017	Multi-countries	NAFLD, HCV, and alcohol-related HCC	Italian (n = 765) and United Kingdom (n = 358) NAFLD patients; combined cohort of chronic hepatitis C (n = 597) or alcoholic liver disease (n = 524)	TaqMan	Additive models	In 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], 2018	Multi-countries	Alcohol-related cirrhotic HCC	751 cases with alcohol-related cirrhosis and HCC and 1165 controls with alcohol-related cirrhosis without HCC	TaqMan	Additive models	The 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], 2019	Thailand	HBV, HCV, and NBNC-related HCC	Healthy controls (n = 105), HBV-related HCC (n = 270), HCV-related HCC (n = 131), and NBNC-related HCC (n = 129)	TaqMan	NA	The 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], 2021	China	Unspecified	779 HCC cases and 1412 cancer-free controls (controls consist of 678 persistent HBV carriers and 734 spontaneously recovered subjects)	MassARRAY	Dominant, additive, recessive, and allelic models	The results suggested no association between MBOAT7-TMC4 rs641738 and HCC risk in most genetic models	The work highlights that MBOAT7-TMC4 rs641738 is not associated with the risk of HCC
Bianco et al[12], 2021	Multi-countries	NAFLD-related HCC	At-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 array	NA	In 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 0.9-1.9	Variants 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], 2022	United Kingdom	MAFLD-related HCC	160979 participants were diagnosed as having MAFLD	United Kingdom BiLEVE and UKBB Axiom array	NA	Model 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: 0.95-1.95	MAFLD 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], 2023	French	Compensated cirrhosis (HCV or alcohol)-related HCC	Cohort 1 (n = 659): Compensated cirrhosis with HCV sustained virologic response. Cohort 2 (n = 486): Compensated alcohol-related cirrhosis	TaqMan	NA	In 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

HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; NAFLD: Nonalcoholic fatty liver disease; HBV: Hepatitis B virus; NBNC: Non-hepatitis B and non-hepatitis C; MAFLD: Metabolic dysfunction-associated fatty liver disease; PRS: Polygenic risk score; OR: Odds ratio; 95%CI: 95% confidence interval; UKBB: United Kingdom Biobank; SNP: Single-nucleotide polymorphism; NA: Not available.