Journal Article

DKFZ-2025-00415

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Association of genetic liability to allergic diseases with overall and early-onset colorectal cancer risk: a Mendelian randomization study.

Alduhayh, S. ; Laskar, R. S. ; Jiang, X. ; Zhu, Z. ; Vincent, E. E. ; Constantinescu, A.-E. ; Buchanan, D. D. ; Grant, R. C. ; Phipps, A. I. ; Brenner, H.DKFZ* ; Huang, W.-Y. ; Kweon, S.-S. ; Li, L. ; Pearlman, R. ; Castellví-Bel, S. ; Gruber, S. B. ; Li, C. I. ; Pellatt, A. ; Platz, E. A. ; Van Guelpen, B. ; Zheng, W. ; Chan, A. T. ; Figueiredo, J. C. ; Ogino, S. ; Ulrich, C. M. ; Gunter, M. J. ; Haycock, P. ; Severi, G. ; Murphy, N. ; Dimou, N.

2025
AACR Philadelphia, Pa.

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Please use a persistent id in citations: doi:10.1158/1055-9965.EPI-24-0970

Abstract: Tumor immunosurveillance theory supports that allergic conditions could decrease cancer risk. However, observational evidence yielded inconsistent results for the association between allergic diseases and colorectal cancer risk. We used Mendelian randomization (MR) to examine potential causal associations of allergies with risk of overall and early-onset colorectal cancer.Genome-wide association study summary statistic data were used to identify genetic variants associated with allergic diseases (Nvariants=65) and individual allergic conditions (asthma, hay fever/allergic rhinitis, eczema). Using two-sample MR, we examined these variants in relation to incident overall (Ncases=52,775 cases) and early-onset colorectal cancer (Ncases=6,176). The mediating role of white blood cells was examined using multivariable MR.In inverse-variance weighted models, genetic liability to allergic diseases was inversely associated with overall (ORper log(odds)= 0.90 [95% CI= 0.85-0.96]; P< 0.01) and early-onset colorectal cancer (OR= 0.83 [95% CI= 0.73-0.95]; P= 0.01). Similar inverse associations were found for hay fever/allergic rhinitis or eczema, while no evidence of association was found between liability to asthma-related phenotypes and colorectal cancer risk. Multivariable MR adjustment for eosinophils weakened the inverse associations for liability to allergic diseases for overall (OR= 0.96 [95% CI= 0.89-1.03]; P= 0.26) and early-onset colorectal cancer (OR= 0.86 [95% CI= 0.73-1.01]; P= 0.06).Our study supports a potential causal association between liability to allergic diseases, specifically hay fever/allergic rhinitis or eczema, and colorectal cancer, possibly at least in part mediated via eosinophil counts.Our results provide evidence that allergic responses may also have a role in immunosurveillance against colorectal cancer.

Note: 2025 May 2;34(5):722-736

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Contributing Institute(s):

1. C070 Klinische Epidemiologie und Alternf. (C070)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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