Journal article
A Comprehensive Assessment of the Causal Relationship Between Atopic Conditions and Pancreatic Cancer Risk: A Two-Sample Mendelian Randomization Study
Cancer epidemiology, biomarkers & prevention, Vol.35(6), pp.1009-1018
06/02/2026
DOI: 10.1158/1055-9965.EPI-25-1601
PMID: 41910234
Abstract
Observational studies consistently report reduced pancreatic ductal adenocarcinoma (PDAC) risk among individuals with atopic conditions (asthma, rhinitis); however, the underlying biological mechanism remains unclear. This Mendelian Randomization (MR) study investigated the potential causal relationship between atopy and PDAC by leveraging multiple genome-wide association studies (GWAS) and individual-level PDAC data.
A two-sample MR analysis was conducted, leveraging genetic variants as instrumental variables for atopic conditions extracted from genomic repositories in Approach 1, and from four large-scale atopy-specific GWAS in Approach 2. SNP-PDAC association estimates were obtained from PanGenEU GWAS. Primary analysis employed the inverse variance weighted (IVW) method. Sensitivity analyses (MR-Egger, weighted median, and leave-one-out) were conducted to evaluate pleiotropy and robustness. Additional IgE-stratified MR analysis was conducted among individuals with biomarker data to explore endotype-specific causality.
There was no clear evidence of a causal association between asthma or rhinitis and PDAC risk (ORasthma range: 0.90-1.07; ORrhinitis range: 0.80-0.98). Sensitivity analyses showed no directional pleiotropy. IgE-stratified analyses exhibited null results for asthma and a modest but insignificant inverse trend for rhinitis among individuals with low IgE sensitization.
This MR study found no evidence supporting a causal protective effect of atopy on PDAC risk. Other factors may modulate the protective effect reported in the observational studies. Atopic endotypes exhibit heterogeneous genetic architectures, warranting further investigation into endotype-specific mechanisms.
These findings shift causal PDAC research toward atopic endotypes.
Details
- Title: Subtitle
- A Comprehensive Assessment of the Causal Relationship Between Atopic Conditions and Pancreatic Cancer Risk: A Two-Sample Mendelian Randomization Study
- Creators
- Jiangchuan He - Spanish National Cancer Research CentreSergio Sabroso-Lasa - Spanish National Cancer Research CentreClaudia Coscia - Spanish National Cancer Research CentreEvangelina López de Maturana - Spanish National Cancer Research CentreLola Alonso - Spanish National Cancer Research CentreRita T Lawlor - University of VeronaAlfredo Carrato - Universidad de AlcaláRafael Alvarez Gallego - Hospital Universitario HM SanchinarroMar Iglesias - Hospital Del MarXavier Molero - Hospital Universitari Arnau de VilanovaChristoph Michalski - Heidelberg UniversityJose Perea - Instituto de Investigación Biomédica de SalamancaMatthias Löhr - Karolinska InstitutetMichael A O'Rorke - University of IowaVictor M Barberá - Hospital General Universitario de ElcheAdonina Tardon - Universidad NebrijaAntoni Farré - Hospital de Sant PauTatjana Crnogorac-Jurcevic - Barts Health NHS TrustEnrique Domínguez-Muñoz - Complejo Hospitalario Universitario de SantiagoThomas M Gress - Philipps University of MarburgWilliam Greenhalf - MerseytravelLinda Sharp - University of Newcastle AustraliaAne Moreno-Oya - Spanish National Cancer Research CentreEithne Costello - University of LiverpoolJorg Kleeff - Martin Luther University Halle-WittenbergBo Kong - Heidelberg UniversityJosefina Mora - Hospital de Sant PauDamian O'Driscoll - University College CorkAldo Scarpa - University of VeronaWeimin Ye - Fujian Medical UniversityFrancisco X Real - Spanish National Cancer Research CentreNuria Malats - Spanish National Cancer Research Centre
- Resource Type
- Journal article
- Publication Details
- Cancer epidemiology, biomarkers & prevention, Vol.35(6), pp.1009-1018
- DOI
- 10.1158/1055-9965.EPI-25-1601
- PMID
- 41910234
- NLM abbreviation
- Cancer Epidemiol Biomarkers Prev
- ISSN
- 1055-9965
- eISSN
- 1538-7755
- Publisher
- American Association for Cancer Research
- Grant note
- European Commission (EC): 018771-MOLDIAG-PACA Ministerio de Ciencia e Innovacin (MCIN): PID2021-128125OB-I00, RTI2018-101071-B-I00 Fondazione AIRC per la ricerca sul cancro ETS (AIRC): 12182 Health Research Board (HRB) Instituto de Salud Carlos III (ISCIII): #PI18/01347, PI21/00495 Cancer Focus Northern Ireland (Cancer Focus NI) Fundacin Cientfica Asociacin Espaola Contra el Cncer (AECC) European Cooperation in Science and Technology (COST): BM1204 ALF - Agreement on Medical Education and Research: SLL20130022
The authors are grateful to all coinvestigators who contributed to the European Study into Digestive Illnesses and Genetics (PanGenEU), listed in the Group Author Collaborators List (Supplementary Materials S1), as well as to the patients, technicians, and field and administrative staff. CNIO coauthors received funding from Accion Estrategica en Salud, Instituto de Salud Carlos III, cofunded by the European Union, ERDF (#PI18/01347, #PI21/00495); Ministerio de Ciencia, Innovacion y Universidades, Madrid, Spain (#RTI2018-101071-B-I00 and #PID2021-128125OB-I00); and Fundacion Cientifica de la AECC, Spain. All authors received funding from the European Cooperation in Science and Technology (COST) Action EUPancreas (#BM1204), the EU-6FP Integrated Project (#018771-MOLDIAG-PACA), and the EU-FP7-HEALTH (#259737-CANCERALIA, #256974-EPC-TM-Net). A. Scarpa and R.T. Lawlor received funding from La Associazione Italiana Ricerca sul Cancro (#12182); L. Sharp and D. O'Driscoll received funding from Cancer Focus Northern Ireland and the Department for Employment and Learning; and M. Lohr received funding from the Health Research Board, Ireland, and ALF (#SLL20130022), Sweden.
- Language
- English
- Electronic publication date
- 03/30/2026
- Date published
- 06/02/2026
- Academic Unit
- Epidemiology; Pathology
- Record Identifier
- 9985149627802771
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