Title :

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

Author(s) :

Trepo, E. [Auteur]
Université libre de Bruxelles [ULB]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Caruso, S [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Yang, J. [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
People's Hospital of Peking University [PKUPH]
Imbeaud, S [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Couchy, G [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Bayard, Q. [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Letouze, E. [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Ganne-Carrie, N [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Hôpital Avicenne [AP-HP]
Moreno, C. [Auteur]
Université libre de Bruxelles [ULB]
Oussalah, A. [Auteur]
Nutrition-Génétique et Exposition aux Risques Environnementaux [NGERE]
Centre Hospitalier Régional Universitaire de Nancy [CHRU Nancy]
Feray, C. [Auteur]
Hôpital Paul Brousse
Blanc, J.F. [Auteur]
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
Bordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
Clément, Bruno [Auteur]
Nutrition, Métabolismes et Cancer [NuMeCan]
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
Centre de Ressources Biologiques Santé [CRB Santé]
Hillon, P [Auteur]
Lipides - Nutrition - Cancer [Dijon - U1231] [LNC]
CHU Dijon
Boursier, J [Auteur]
Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques [HIFIH]
Centre Hospitalier Universitaire d'Angers [CHU Angers]
Paradis, V. [Auteur]
Hôpital Beaujon [AP-HP]
Calderaro, J. [Auteur]
Institut Mondor de Recherche Biomédicale [IMRB]
Hôpital Henri Mondor
Gnemmi, V. [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Nault, J.-C. [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Hôpital Avicenne [AP-HP]
Gueant, J.-L. [Auteur]
Centre Hospitalier Régional Universitaire de Nancy [CHRU Nancy]
Nutrition-Génétique et Exposition aux Risques Environnementaux [NGERE]
Deviere, J. [Auteur]
Université libre de Bruxelles [ULB]
Archambeaud, I [Auteur]
Institut des Maladies de l'Appareil Digestif
Hôtel-Dieu de Nantes
Vitellius, C. [Auteur]
Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques [HIFIH]
Centre Hospitalier Universitaire d'Angers [CHU Angers]
Turlin, B. [Auteur]
Nutrition, Métabolismes et Cancer [NuMeCan]
Centre de Ressources Biologiques Santé [CRB Santé]
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
Bronowicki, J.-P. [Auteur]
Centre Hospitalier Régional Universitaire de Nancy [CHRU Nancy]
Nutrition-Génétique et Exposition aux Risques Environnementaux [NGERE]
Gustot, T. [Auteur]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]
Université libre de Bruxelles [ULB]
Sutton, A. [Auteur]
Laboratoire de Recherche Vasculaire Translationnelle [LVTS (UMR_S_1148 / U1148)]
Hôpital Avicenne [AP-HP]
Ziol, M [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Nahon, P. [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Hôpital Avicenne [AP-HP]
Zucman-Rossi, J [Auteur correspondant]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Hôpital Européen Georges Pompidou [APHP] [HEGP]

Journal title :

Lancet Oncology

Pages :

161-171

Publisher :

Elsevier

Publication date :

2022-01

ISSN :

1470-2045

HAL domain(s) :

Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]/Cancer

English abstract : [en]

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 ...
Show more >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 (pandlt;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 hepatocellular carcinoma risk at TM6SF2 (rs58542926; p=6·02 × 10−10), PNPLA3 (rs738409; p=9·29 × 10−7), and HSD17B13 (rs72613567; p=2·49 × 10−4). The validation cohort included 874 cases and 1059 controls and three variants were replicated: WNT3A-WNT9A (rs708113; p=1·17 × 10−3), TM6SF2 (rs58542926; p=4·06 × 10−5), and PNPLA3 (rs738409; p=1·17 × 10−4). All three variants reached GWAS significance in the meta-analysis: WNT3A-WNT9A (odds ratio 0·73, 95% CI 0·66–0·81; p=3·93 × 10−10), TM6SF2 (1·77, 1·52–2·07; p=3·84×10−13), PNPLA3 (1·34, 1·22–1·47; p=7·30 × 10−10). Adjustment for clinical covariates yielded similar results. We observed an additive effect of at-risk alleles on alcohol-related hepatocellular carcinoma. WNT3A-WNT9A rs708113 was not associated with liver fibrosis. Interpretation: WNT3A-WNT9A is a susceptibility locus for alcohol-related hepatocellular carcinoma, suggesting an early role of the Wnt–β-catenin pathway in alcohol-related hepatocellular carcinoma carcinogenesis.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

ANR Project :

Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL