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RESEARCH PRODUCT
MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals
Paula IruzubietaLuca MieleSalvatore PettaBenedetta DonatiAnna Ludovica FracanzaniMisti Vanette MccainMisti Vanette MccainStefano Ginanni CorradiniStefania GrimaudoPaola DongiovanniGiorgio SoardoStefano RomeoStefano RomeoMassimo ColomboAntonio GriecoChiara RossoAlessio AghemoRenato RomagnoliHelen L. ReevesHelen L. ReevesEster VanniLaura De LucaLuca ValentiRosellina Margherita MancinaFabio ColliQuentin M. AnsteeQuentin M. AnsteeFlaminia FerriAntonio CraxìS. MaierMarica MeroniElisabetta BugianesiSilvia Fargionsubject
0301 basic medicineLiver CirrhosisMaleAlcoholic liver diseasePathologyCirrhosisliver diseasesGastroenterology0302 clinical medicineSettore BIO/13 - Biologia ApplicataNon-alcoholic Fatty Liver DiseaseRisk FactorsNonalcoholic fatty liver diseasefatty liver-disease; cirrhosis; liver cancer; hepatitis C; hepatocellular carcinoma; liver diseases; fibrosis; carcinogenesis; fatty liver; allelesHCCProspective cohort studySettore MED/12 - GastroenterologiaMultidisciplinaryLiver NeoplasmsQRhepatocellular carcinomaSingle NucleotideMiddle Aged3. Good healthItalyfatty liver-diseaseHepatocellular carcinomaCohortMedicine030211 gastroenterology & hepatologyFemalecarcinogenesisAcyltransferases; Adult; Aged; Carcinoma Hepatocellular; Female; Gene Expression Regulation; Genotype; Humans; Italy; Liver Cirrhosis; Liver Neoplasms; Male; Membrane Proteins; Middle Aged; Non-alcoholic Fatty Liver Disease; Polymorphism Single Nucleotide; Risk Factors; Alleles; Genetic Association Studies; Genetic Predisposition to Disease; Genetic VariationAdultmedicine.medical_specialtyCarcinoma HepatocellularGenotypeSciencePolymorphism Single NucleotideArticleliver cancer03 medical and health sciencesInternal medicinemedicineHumansGenetic Predisposition to DiseaseAllelePolymorphismAllelesGenetic Association Studiesfatty liverAgedSettore MED/06 - ONCOLOGIA MEDICAbusiness.industrycirrhosisfibrosisCarcinomaGenetic VariationMembrane ProteinsHepatocellularmedicine.diseasedigestive system diseases030104 developmental biologyGene Expression Regulationhepatitis CbusinessAcyltransferasesTM6SF2description
AbstractNonalcoholic fatty liver disease (NAFLD) represents an emerging cause of hepatocellular carcinoma (HCC), especially in non-cirrhotic individuals. The rs641738 C > T MBOAT7/TMC4 variant predisposes to progressive NAFLD, but the impact on hepatic carcinogenesis is unknown. In Italian NAFLD patients, the rs641738 T allele was associated with NAFLD-HCC (OR 1.65, 1.08–2.55; n = 765), particularly in those without advanced fibrosis (p < 0.001). The risk T allele was linked to 3’-UTR variation in MBOAT7 and to reduced MBOAT7 expression in patients without severe fibrosis. The number of PNPLA3, TM6SF2, and MBOAT7 risk variants was associated with NAFLD-HCC independently of clinical factors (p < 0.001), but did not significantly improve their predictive accuracy. When combining data from an independent UK NAFLD cohort, in the overall cohort of non-cirrhotic patients (n = 913, 41 with HCC) the T allele remained associated with HCC (OR 2.10, 1.33–3.31). Finally, in a combined cohort of non-cirrhotic patients with chronic hepatitis C or alcoholic liver disease (n = 1121), the T allele was independently associated with HCC risk (OR 1.93, 1.07–3.58). In conclusion, the MBOAT7 rs641738 T allele is associated with reduced MBOAT7 expression and may predispose to HCC in patients without cirrhosis, suggesting it should be evaluated in future prospective studies aimed at stratifying NAFLD-HCC risk.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-07-01 | Scientific Reports |