RT Journal Article
T1 Deciphering the complex interplay between pancreatic cancer, diabetes mellitus subtypes and obesity/BMI through causal inference and mediation analyses.
A1 Molina-Montes, Esther
A1 Coscia, Claudia
A1 Gómez-Rubio, Paulina
A1 Fernández, Alba
A1 Boenink, Rianne
A1 Rava, Marta
A1 Márquez, Mirari
A1 Molero, Xavier
A1 Löhr, Matthias
A1 Sharp, Linda
A1 Michalski, Christoph W
A1 Farré, Antoni
A1 Perea, José
A1 O'Rorke, Michael
A1 Greenhalf, William
A1 Iglesias, Mar
A1 Tardón, Adonina
A1 Gress, Thomas M
A1 Barberá, Victor M
A1 Crnogorac-Jurcevic, Tatjana
A1 Muñoz-Bellvís, Luis
A1 Dominguez-Muñoz, J Enrique
A1 Renz, Harald
A1 Balcells, Joaquim
A1 Costello, Eithne
A1 Ilzarbe, Lucas
A1 Kleeff, Jörg
A1 Kong, Bo
A1 Mora, Josefina
A1 O'Driscoll, Damian
A1 Poves, Ignasi
A1 Scarpa, Aldo
A1 Yu, Jingru
A1 Hidalgo, Manuel
A1 Lawlor, Rita T
A1 Ye, Weimin
A1 Carrato, Alfredo
A1 Real, Francisco X
A1 Malats, Núria
A1 PanGenEU Study Investigators, 
K1 cancer epidemiology
K1 diabetes mellitus
K1 obesity
K1 pancreatic cancer
AB To characterise the association between type 2 diabetes mellitus (T2DM) subtypes (new-onset T2DM (NODM) or long-standing T2DM (LSDM)) and pancreatic cancer (PC) risk, to explore the direction of causation through Mendelian randomisation (MR) analysis and to assess the mediation role of body mass index (BMI). Information about T2DM and related factors was collected from 2018 PC cases and 1540 controls from the PanGenEU (European Study into Digestive Illnesses and Genetics) study. A subset of PC cases and controls had glycated haemoglobin, C-peptide and genotype data. Multivariate logistic regression models were applied to derive ORs and 95% CIs. T2DM and PC-related single nucleotide polymorphism (SNP) were used as instrumental variables (IVs) in bidirectional MR analysis to test for two-way causal associations between PC, NODM and LSDM. Indirect and direct effects of the BMI-T2DM-PC association were further explored using mediation analysis. T2DM was associated with an increased PC risk when compared with non-T2DM (OR=2.50; 95% CI: 2.05 to 3.05), the risk being greater for NODM (OR=6.39; 95% CI: 4.18 to 9.78) and insulin users (OR=3.69; 95% CI: 2.80 to 4.86). The causal association between T2DM (57-SNP IV) and PC was not statistically significant (ORLSDM=1.08, 95% CI: 0.86 to 1.29, ORNODM=1.06, 95% CI: 0.95 to 1.17). In contrast, there was a causal association between PC (40-SNP IV) and NODM (OR=2.85; 95% CI: 2.04 to 3.98), although genetic pleiotropy was present (MR-Egger: p value=0.03). Potential mediating effects of BMI (125-SNPs as IV), particularly in terms of weight loss, were evidenced on the NODM-PC association (indirect effect for BMI in previous years=0.55). Findings of this study do not support a causal effect of LSDM on PC, but suggest that PC causes NODM. The interplay between obesity, PC and T2DM is complex.
YR 2020
FD 2020-05-14
LK https://hdl.handle.net/10668/26702
UL https://hdl.handle.net/10668/26702
LA en
DS RISalud
RD Apr 12, 2025