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Molina-Montes, Esther; Coscia, Claudia; Gómez-Rubio, Paulina; Fernández, Alba; Boenink, Rianne; Rava, Marta; Márquez, Mirari; Molero, Xavier; Löhr, Matthias; Sharp, Linda; Michalski, Christoph W; Farré, Antoni; Perea, José; O’Rorke, Michael; Greenhalf, William; Iglesias, Mar; Tardón, Adonina; Gress, Thomas M; Barberá, Victor M; Crnogorac-Jurcevic, Tatjana; Muñoz-Bellvís, Luis; Dominguez-Muñoz, J Enrique; Renz, Harald; Balcells, Joaquim; [...]

Deciphering the complex interplay between pancreatic cancer, diabetes mellitus subtypes and obesity/BMI through causal inference and mediation analyses

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  • Medientyp: E-Artikel
  • Titel: Deciphering the complex interplay between pancreatic cancer, diabetes mellitus subtypes and obesity/BMI through causal inference and mediation analyses
  • Beteiligte: Molina-Montes, Esther; Coscia, Claudia; Gómez-Rubio, Paulina; Fernández, Alba; Boenink, Rianne; Rava, Marta; Márquez, Mirari; Molero, Xavier; Löhr, Matthias; Sharp, Linda; Michalski, Christoph W; Farré, Antoni; Perea, José; O’Rorke, Michael; Greenhalf, William; Iglesias, Mar; Tardón, Adonina; Gress, Thomas M; Barberá, Victor M; Crnogorac-Jurcevic, Tatjana; Muñoz-Bellvís, Luis; Dominguez-Muñoz, J Enrique; Renz, Harald; Balcells, Joaquim; [...]
  • Erschienen: BMJ, 2020
  • Erschienen in: Gut
  • Sprache: Englisch
  • DOI: 10.1136/gutjnl-2019-319990
  • ISSN: 0017-5749; 1468-3288
  • Schlagwörter: Gastroenterology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:sec><jats:title>Objectives</jats:title><jats:p>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).</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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 (OR<jats:sub>LSDM</jats:sub>=1.08, 95% CI: 0.86 to 1.29, OR<jats:sub>NODM</jats:sub>=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).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>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.</jats:p></jats:sec>