Association of genetic liability to allergic diseases with overall and early-onset colorectal cancer risk: a Mendelian randomization study.

IF 3.7 3区医学 Q2 ONCOLOGY Cancer Epidemiology Biomarkers & Prevention Pub Date : 2025-02-21 DOI:10.1158/1055-9965.EPI-24-0970

Saleh Alduhayh, Ruhina Shirin Laskar, Xia Jiang, Zhaozhong Zhu, Emma E Vincent, Andrei-Emil Constantinescu, Daniel D Buchanan, Robert C Grant, Amanda I Phipps, Hermann Brenner, Wen-Yi Huang, Sun-Seog Kweon, Li Li, Rachel Pearlman, Sergi Castellví-Bel, Stephen B Gruber, Christopher I Li, Andrew Pellatt, Elizabeth A Platz, Bethany Van Guelpen, Wei Zheng, Andrew T Chan, Jane C Figueiredo, Shuji Ogino, Cornelia M Ulrich, Marc J Gunter, Philip Haycock, Gianluca Severi, Neil Murphy, Niki Dimou

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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Impact: Our results provide evidence that allergic responses may also have a role in immunosurveillance against colorectal cancer.

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来源期刊

Cancer Epidemiology Biomarkers & Prevention 医学-公共卫生、环境卫生与职业卫生

CiteScore

6.50

自引率

2.60%

发文量

538

审稿时长

1.6 months

期刊介绍： Cancer Epidemiology, Biomarkers & Prevention publishes original peer-reviewed, population-based research on cancer etiology, prevention, surveillance, and survivorship. The following topics are of special interest: descriptive, analytical, and molecular epidemiology; biomarkers including assay development, validation, and application; chemoprevention and other types of prevention research in the context of descriptive and observational studies; the role of behavioral factors in cancer etiology and prevention; survivorship studies; risk factors; implementation science and cancer care delivery; and the science of cancer health disparities. Besides welcoming manuscripts that address individual subjects in any of the relevant disciplines, CEBP editors encourage the submission of manuscripts with a transdisciplinary approach.