| Title: | Low type-2 immune effectors modulate atopic diseases' protective role in pancreatic cancer risk |
| Journal: | International Journal of Cancer |
| Published: | 18 Mar 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40098454/ |
| DOI: | https://doi.org/10.1002/ijc.35397 |
Publication 15575
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
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 × 109 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.</p>
26 Authors
- 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
- the PanGenEU Study Investigators
1 Application
| Application ID | Title |
|---|---|
| 94757 | Deciphering the complex relationship between asthma/allergy and pancreatic cancer risk |
Enabling scientific discoveries that improve human health