Low type‐2 immune effectors modulate atopic diseases' protective role in pancreatic cancer risk

Jiangchuan He; Bilal Alashkar Alhamwe; Sergio Sabroso; Alfredo Carrato; Manuel Hidalgo; Xavier Molero; Mar Iglesias; José Perea; Antoni Farré; Adonina Tardón; Enrique Dominguez-Muñoz; Victor Barberà; Luís Muñoz-Bellvís; Matthias Löhr; William Greenhalf; Michael O'Rorke; Thomas Gress; Tatjana Crnogorac-Jurcevic; Auba Gayà; Alberto Langtry; Jörg Kleeff; Rita Lawlor; Francisco X. Real; Harald Renz; Núria Malats; PanGenEU Study Investigators

doi:10.1002/ijc.35397

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Low type‐2 immune effectors modulate atopic diseases' protective role in pancreatic cancer risk

Journal article

Peer reviewed

Low type‐2 immune effectors modulate atopic diseases' protective role in pancreatic cancer risk

Jiangchuan He, Bilal Alashkar Alhamwe, Sergio Sabroso, Alfredo Carrato, Manuel Hidalgo, Xavier Molero, Mar Iglesias, José Perea, Antoni Farré, Adonina Tardón, …

International journal of cancer, Vol.157(3), pp.468-479

08/2025

DOI: 10.1002/ijc.35397

PMID: 40098454

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Abstract

Studies reported that atopic individuals exhibit a 36% reduced risk of developing pancreatic ductal adenocarcinoma (PDAC); however, the underlying molecular mechanisms remain unclear. This study examines the specific role of type‐2 immune response in the atopy–PDAC inverse association. To endotype atopic conditions using type‐2 immune effectors (i.e., eosinophils and immunoglobulin‐E[IgE]) and investigate their protective effect against PDAC risk, IgE levels were measured in 688 PDAC cases and 558 controls from the PanGenEU case–control study. ‘IgE‐sensitization’ was defined as having >100 kU/L total IgE with lab‐tested sensitization to ≥1 food‐ or aeroallergens. Atopic conditions were determined using the European Community Respiratory Health Survey questionnaire. The UK Biobank cohort's 544 PDAC cases and 92,038 nested controls were categorized based on a threshold of 0.15 × 10 9 eosinophil cells/L plus self‐reported atopy. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using multivariable logistic regression. Restricted cubic splines were applied to examine the nonlinear relationship between type‐2 immune effectors and PDAC risk. PDAC risk was not linearly associated with type‐2 immune effectors levels. Compared to low IgE‐sensitized non‐atopic individuals, the low IgE‐sensitized atopic population had significantly reduced PDAC risk (OR = 0.56, 95% CI: 0.35–0.84). Similar trends were observed among atopic individuals with low eosinophil counts (OR = 0.67, 95% CI: 0.47–0.95). Atopic conditions were inversely associated with PDAC risk, particularly among those with low levels of type‐2 immune effectors. This indicates the protective effect of atopy against PDAC risk is modulated by low type‐2 immune response.

Asthma

Pancreatic Cancer

allergy

blood eosinophils

serum IgE

type-2 immunity

Details

Title: Subtitle: Low type‐2 immune effectors modulate atopic diseases' protective role in pancreatic cancer risk
Creators: Jiangchuan He - Spanish National Cancer Research Centre
Bilal Alashkar Alhamwe - Philipps University of Marburg
Sergio Sabroso - Spanish National Cancer Research Centre
Alfredo Carrato - Hospital Universitario Ramón y Cajal
Manuel Hidalgo - Cornell University
Xavier Molero - Vall d'Hebron Hospital Universitari
Mar Iglesias - Parc de Salut
José Perea - Research Institute Hospital 12 de Octubre
Antoni Farré - Hospital de Sant Pau
Adonina Tardón - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Enrique Dominguez-Muñoz - Universidade de Santiago de Compostela
Victor Barberà - Hospital General Universitario de Elche
Luís Muñoz-Bellvís - Complejo Hospitalario de Salamanca
Matthias Löhr - Karolinska University Hospital
William Greenhalf - University of Liverpool
Michael O'Rorke - University of Iowa
Thomas Gress - Philipps University of Marburg
Tatjana Crnogorac-Jurcevic - Queen Mary University of London
Auba Gayà - Spanish National Cancer Research Centre
Alberto Langtry - Spanish National Cancer Research Centre
Jörg Kleeff - Technical University of Munich
Rita Lawlor - University of Verona
Francisco X. Real - Spanish National Cancer Research Centre
Harald Renz - Philipps University of Marburg
Núria Malats - Spanish National Cancer Research Centre
PanGenEU Study Investigators
Resource Type: Journal article
Publication Details: International journal of cancer, Vol.157(3), pp.468-479
DOI: 10.1002/ijc.35397
PMID: 40098454
NLM abbreviation: Int J Cancer
ISSN: 0020-7136
eISSN: 1097-0215
Publisher: WILEY
Grant note: Deutsches Zentrum fr Lungenforschung: 94757
The authors are thankful to the coordinators, field and administrative workers, technicians, and study participants of the European Study into Digestive Illnesses and Genetics (PanGenEU) study. This research has been conducted using the UK Biobank Resource under Application Number 94757.
Language: English
Electronic publication date: 03/18/2025
Date published: 08/2025
Academic Unit: Epidemiology; Pathology
Record Identifier: 9984801617002771

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