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

Oussalah, Abderrahim; Avogbe, Patrice Hodonou

doi:10.18632/oncotarget.11327

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Title		BRIP1 coding variants are associated with a high risk of hepatocellular carcinoma occurrence in patients with HCV- or HBV-related liver disease
Authors		Oussalah, Abderrahim Avogbe, Patrice Hodonou
Collaboration		CiRCE Study Group With : Negro, Francesco / Bochud, Pierre-Yves
Published in		Oncotarget. 2017, vol. 8, p. 62842-62857
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.
Keywords		DNA repair genes — Hepatocellular carcinoma — BRIP1 — Hepatitis B virus — Hepatitis C virus
Identifiers		DOI: 10.18632/oncotarget.11327 PMID: 27542272
Full text		Article (Published version) (2.8 MB) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research group		Etudes et traitement de l'hépatite C et B (554)
Citation (ISO format)		OUSSALAH, Abderrahim, AVOGBE, Patrice Hodonou. BRIP1 coding variants are associated with a high risk of hepatocellular carcinoma occurrence in patients with HCV- or HBV-related liver disease. In: Oncotarget, 2017, vol. 8, p. 62842-62857. doi: 10.18632/oncotarget.11327 https://archive-ouverte.unige.ch/unige:89019