Analysis of exposome and genetic variability suggests stress as a major contributor for development of pancreatic ductal adenocarcinoma.

Cancer Gene-environment interaction Polygenic risk score SNPs UK Biobank

Journal

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
ISSN: 1878-3562
Titre abrégé: Dig Liver Dis
Pays: Netherlands
ID NLM: 100958385

Informations de publication

Date de publication:
18 Nov 2023
Historique:
received: 03 07 2023
revised: 05 10 2023
accepted: 18 10 2023
medline: 21 11 2023
pubmed: 21 11 2023
entrez: 20 11 2023
Statut: aheadofprint

Résumé

The current knowledge on pancreatic ductal adenocarcinoma (PDAC) risk factors is limited and no study has comprehensively tested the exposome in combination with the genetic variability in relation to the disease susceptibility. The aim of this study was to analyze the exposome and its interaction with known genetic susceptibility loci, in relation to PDAC risk. A case-control study nested in UK Biobank cohort was conducted on 816 PDAC cases and 302,645 controls. A total of 347 exposure variables, and a polygenic risk score (PRS) were analyzed through logistic regression. Gene-environment interaction analyses were conducted. A total of 52 associations under the Bonferroni corrected threshold of p < 1.46 × 10 In conclusion, our results suggest that a stressful lifestyle and sedentary behaviors may play a major role in PDAC susceptibility independently from the genetic background.

Sections du résumé

BACKGROUND BACKGROUND
The current knowledge on pancreatic ductal adenocarcinoma (PDAC) risk factors is limited and no study has comprehensively tested the exposome in combination with the genetic variability in relation to the disease susceptibility.
AIM OBJECTIVE
The aim of this study was to analyze the exposome and its interaction with known genetic susceptibility loci, in relation to PDAC risk.
METHODS METHODS
A case-control study nested in UK Biobank cohort was conducted on 816 PDAC cases and 302,645 controls. A total of 347 exposure variables, and a polygenic risk score (PRS) were analyzed through logistic regression. Gene-environment interaction analyses were conducted.
RESULTS RESULTS
A total of 52 associations under the Bonferroni corrected threshold of p < 1.46 × 10
CONCLUSION CONCLUSIONS
In conclusion, our results suggest that a stressful lifestyle and sedentary behaviors may play a major role in PDAC susceptibility independently from the genetic background.

Identifiants

pubmed: 37985251
pii: S1590-8658(23)01004-6
doi: 10.1016/j.dld.2023.10.015
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Conflict of interest All the authors have no conflicts of interest to declare.

Auteurs

Giulia Peduzzi (G)

Department of Biology, University of Pisa, Via Luca Ghini, 13, 56126 Pisa, Italy.

Alessio Felici (A)

Department of Biology, University of Pisa, Via Luca Ghini, 13, 56126 Pisa, Italy.

Roberto Pellungrini (R)

Classe di scienze, Scuola Normale Superiore, Piazza dei Cavalieri, 7, 56126 Pisa, Italy.

Francesca Giorgolo (F)

Kode s.r.l., Lungarno Galileo Galilei 1, 56125 Pisa, Italy.

Riccardo Farinella (R)

Department of Biology, University of Pisa, Via Luca Ghini, 13, 56126 Pisa, Italy.

Manuel Gentiluomo (M)

Department of Biology, University of Pisa, Via Luca Ghini, 13, 56126 Pisa, Italy.

Andrea Spinelli (A)

Kode s.r.l., Lungarno Galileo Galilei 1, 56125 Pisa, Italy.

Gabriele Capurso (G)

Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy.

Anna Monreale (A)

Department of Computer Science, University of Pisa, Largo Bruno Pontecorvo 3, 56127 Pisa, Italy.

Federico Canzian (F)

Genomic Epidemiology Group, German Cancer Research Center, (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

Marco Calderisi (M)

Kode s.r.l., Lungarno Galileo Galilei 1, 56125 Pisa, Italy.

Daniele Campa (D)

Department of Biology, University of Pisa, Via Luca Ghini, 13, 56126 Pisa, Italy. Electronic address: daniele.campa@unipi.it.

Classifications MeSH