Common genetic variation in alcohol-related hepatocellular carcinoma: a case-control genome-wide association study.

作者：Eric Trépo, Stefano Caruso, Jie Yang, Sandrine Imbeaud, Gabrielle Couchy, Quentin Bayard, Éric Letouzé, Nathalie Ganne‐Carrié, Christophe Moreno, Abderrahim Oussalah, Cyrille Féray, Jean Frédéric Blanc, Bruno Clément, Patrick Hillon, Jérôme Boursier, Valérie Paradis, Julien Caldéraro, Viviane Gnemmi, Nault, J-C. (J.-C.), Jean‐Louis Guéant, Jacques Devière, Isabelle Archambeaud, Carole Vitellius, Bruno Turlin, Jean–Pierre Bronowicki, Thierry Gustot, Angéla Sutton, Meiller, C. (C.), Cao, Q. (Q.), Hirsch, T. (T.Z.), Rebouissou, S. (S.), Degré, D. (D.), Otero Sanchez, L. (L.), Rosewick, N. (N.), Quertinmont, E. (E.), Desille-Dugast, M. (M.), François-Vié, M. (M.), Moins, C. (C.), Leteurtre, E. (E.), Lassailly, G. (G.), Ningarhari, M. (M.), Boleslawski, E. (E.), Cottet, V. (V.), Ziol, M. (M), Nahon, P. (P.), Zucman-Rossi, J. (J) · 发表于：Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) · 年份：2021 · 被引用次数：75 · 研究领域：Liver Disease Diagnosis and Treatment、Alcohol Consumption and Health Effects、Hepatocellular Carcinoma Treatment and Prognosis

Background: Hepatocellular carcinoma is a frequent consequence of alcohol-related liver disease, with variable incidence among heavy drinkers. We did a genome-wide association study (GWAS) to identify common genetic variants for alcohol-related hepatocellular carcinoma.Methods: We conducted a two-stage case-control GWAS in a discovery cohort of 2107 unrelated European patients with alcohol-related liver disease aged 20–92 years recruited between Oct 22, 1993, and March 12, 2017. Cases were patients with alcohol-related hepatocellular carcinoma diagnosed by imaging or histology. Controls were patients with alcohol-related liver disease without hepatocellular carcinoma. We used an additive logistic regression model adjusted for the first ten principal components to assess genetic variants associated with alcohol-related hepatocellular carcinoma. We did another analysis with adjustment for age, sex, and liver fibrosis. New candidate associations (p<1 × 10−6) and variants previously associated with alcohol-related hepatocellular carcinoma were evaluated in a validation cohort of 1933 patients with alcohol-related liver disease aged 29–92 years recruited between July 21, 1995, and May 2, 2019. We did a meta-analysis of the two case–control cohorts.Findings: The discovery cohort included 775 cases and 1332 controls. Of 7 962 325 variants assessed, we identified WNT3A-WNT9A (rs708113; p=1·11 × 10−8) and found support for previously reported regions associated with alcohol-related...