Publications Scientifiques

[ Article ] BRIP1 coding variants are associated with a high risk of hepatocellular carcinoma occurrence in patients with HCV- or HBV-related liver disease

Date de soumission: 07-02-2018
Année de Publication: 2016
Entité/Laboratoire Laboratoire de Biochimie et de Biologie Moléculaire (LBBM)
Document type : Article
Discipline(s) : Oncologie
Titre BRIP1 coding variants are associated with a high risk of hepatocellular carcinoma occurrence in patients with HCV- or HBV-related liver disease
Auteurs Oussalah Abderrahim [1], Avogbe Hodonou Patrice [1], Guyot Erwan [3], Chery Céline [4], Guéant-Rodriguez Rosa-Maria [5], Ganne-Carrié Nathalie [6],
Journal: Oncotarget
Catégorie Journal: Internationale
Impact factor: 5.312
Volume Journal: 8
DOI:
Resume The molecular mechanisms of hepatocellular carcinoma (HCC) carcinogenesis are still not fully understood. DNA repair defects may in uence HCC risk. The aim of the study was to look for potential genetic variants of DNA repair genes associated with HCC risk among patients with alcohol- or viral-induced liver disease. We performed four case-control studies on 2,006 European- (Derivation#1 and #2 studies) and African-ancestry (Validation#1 and #2 studies) patients originating from several cohorts in order to assess the association between genetic variants on DNA repair genes and HCC risk using a custom array encompassing 94 genes. In the Derivation#1 study, the BRIP1 locus reached array-wide signi cance (Chi-squared SV-Perm, P=5.00×10–4) among the 253 haplotype blocks tested for their association with HCC risk, in patients with viral cirrhosis but not among those with alcoholic cirrhosis. The BRIP1 haplotype block included three exonic variants (rs4986763, rs4986764, rs4986765). The BRIP1 ‘AAA’ haplotype was signi cantly associated with an increased HCC risk [odds ratio (OR), 2.01 (1.19–3.39); false discovery rate (FDR)-P=1.31×10–2]. In the Derivation#2 study, results were con rmed for the BRIP1 ‘GGG’ haplotype [OR, 0.53 (0.36–0.79); FDR-P=3.90×10–3]. In both Validation#1 and #2 studies, BRIP1 ‘AAA’ haplotype was signi cantly associated with an increased risk of HCC [OR, 1.71 (1.09–2.68); FDR-P=7.30×10–2; and OR, 6.45 (4.17–9.99); FDR-P=2.33×10–19, respectively]. Association between the BRIP1 locus and HCC risk suggests that impaired DNA mismatch repair might play a role in liver carcinogenesis, among patients with HCV- or HBV-related liver disease.
Mots clés Hepatocellular carcinoma, DNA repair genes, BRIP1, HBV, HCV
Pages 62842 - 62857
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