Mendelian randomisation study of the effects of known and putative risk factors on pancreatic cancer

• Verfasst von: Lu, Ye [VerfasserIn]
• Verfasst von: Gentiluomo, Manuel [VerfasserIn]
• Verfasst von: Lorenzo Bermejo, Justo [VerfasserIn]
• Verfasst von: Morelli, Luca [VerfasserIn]
• Verfasst von: Obazee, Ofure [VerfasserIn]
• Verfasst von: Campa, Daniele [VerfasserIn]
• Verfasst von: Canzian, Federico [VerfasserIn]
• Titel: Mendelian randomisation study of the effects of known and putative risk factors on pancreatic cancer
• Verf.angabe: Ye Lu, Manuel Gentiluomo, Justo Lorenzo-Bermejo, Luca Morelli, Ofure Obazee, Daniele Campa, Federico Canzian
• E-Jahr: 2020
• Jahr: 17 February 2020
• Umfang: 9 S.
• Fussnoten: Gesehen am 02.02.2021
• Titel Quelle: Enthalten in: Journal of medical genetics
• Ort Quelle: London : BMJ Publishing Group, 1964
• Jahr Quelle: 2020
• Band/Heft Quelle: 57(2020), 12, Seite 820-828
• ISSN Quelle: 1468-6244
• DOI: doi:10.1136/jmedgenet-2019-106200
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: genetic polymorphisms
• Sach-SW: Mendelian randomization
• Sach-SW: pancreatic cancer
• Sach-SW: risk factors
• K10plus-PPN: 174671218X

Abstract

Background Observational studies have reported multiple risk factors for pancreatic ductal adenocarcinoma (PDAC). Some are well established, like tobacco smoking, alcohol drinking, obesity and type 2 diabetes, whereas some others are putative, such as allergy and dietary factors. Identifying causal risk factors can help establishing those that can be targeted to contribute to prevent PDAC. - Objective We sought to investigate the possible causal effects of established and putative factors on PDAC risk. - Methods We conducted a two-sample Mendelian randomisation (MR) study using publicly available data for genetic variants associated with the factors of interest, and summary genetic data from genome-wide association studies of the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including in total 8769 cases and 7055 controls. Causality was assessed using inverse-variance weighted, MR-Egger regression and weighted median methods, complemented with sensitivity and radial MR analyses. - Results We found evidence for a causal effect of body mass index (BMI) on PDAC risk (OR 1.43, 95% CI 1.20 to 1.71, p=8.43×10−5). Fasting insulin (OR 2.84, 95% CI 1.23 to 6.56, p=0.01), low-density lipoprotein cholesterol (OR 1.16, 95% CI 1.02 to 1.32, p=0.03) and type 2 diabetes (OR 1.09, 95% CI 1.01 to 1.17, p=0.02) were also causally associated with PDAC risk. BMI showed both direct and fasting insulin-mediated causal effects. - Conclusion We found strong evidence that BMI is causally associated with PDAC risk, providing support that obesity management may be a potential prevention strategy for reducing pancreatic cancer risk while fasting insulin and type 2 diabetes showed a suggestive association that should be further investigated.