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

Abderrahim Oussalah 1, 2 Patrice Hodonou Avogbe 1 Erwan Guyot 3, 4 Céline Chery 1, 2 Rosa-Maria Guéant 1, 2 Nathalie Ganne-Carrié 4, 5 Aurélie Cobat 6, 7 Darius Moradpour 8 Bertrand Nalpas 9, 10 Francesco Negro 11 Thierry Poynard 12 Stanislas Pol 13 Pierre Bochud 8 Laurent Abel 7, 14 Hélène Jeulin 15 Evelyne Schvoerer 16, 17 Nicodème Chabi 1 Emile Amouzou 18 Ambaliou Sanni 19 Hélène Barraud 20 Pierre Rouyer 1 Thomas Josse 1 Laetitia Goffinet 1 Jean-Louis Jouve 21 Anne Minello 21 Claire Bonithon-Kopp 21 Gérard Thiefin 22 Vincent Di Martino 23 Michel Doffoël 24 Carine Richou 25 Jean-Jacques Raab 26 Patrick Hillon 21 Jean-Pierre Bronowicki 1, 2 Jean-Louis Guéant 1, 2, *
Abstract : The molecular mechanisms of hepatocellular carcinoma (HCC) carcinogenesis are still not fully understood. DNA repair defects may influence 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 significance (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 significantly 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 confirmed 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 significantly 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.
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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01494359
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Dernière modification le : mardi 27 octobre 2020 - 14:34:43
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Abderrahim Oussalah, Patrice Hodonou Avogbe, Erwan Guyot, Céline Chery, Rosa-Maria Guéant, et al.. BRIP1 coding variants are associated with a high risk of hepatocellular carcinoma occurrence in patients with HCV- or HBV-related liver disease.. Oncotarget, Impact journals, 2016, 8 (38), pp.62842-62857. ⟨10.18632/oncotarget.11327⟩. ⟨hal-01494359⟩

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