Association of Genetic Liability to Allergic Diseases with Overall and Early-Onset Colorectal Cancer Risk: a Mendelian randomization study

Saleh Alduhayh; Ruhina Shirin Laskar; Xia Jiang; Zhaozhong Zhu; Emma E Vincent; Andrei 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 J Pellatt; Elizabeth A. Platz; Bethany Van Guelpen; Wei  Zheng; Andrew T. Chan; Jane C. Figueiredo; Shuji Ogino; Cornelia M Ulrich; Marc J.  Gunter; Philip C Haycock; Gianluca Severi; Neil   Murphy; Niki L Dimou

doi:10.1158/1055-9965.EPI-24-0970

Association of Genetic Liability to Allergic Diseases with Overall and Early-Onset Colorectal Cancer Risk: a Mendelian randomization study

Saleh Alduhayh, Ruhina Shirin Laskar, Xia Jiang, Zhaozhong Zhu, Emma E Vincent, Andrei 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 J Pellatt, Elizabeth A. Platz, Bethany Van GuelpenWei Zheng, Andrew T. Chan, Jane C. Figueiredo, Shuji Ogino, Cornelia M Ulrich, Marc J. Gunter , Philip C Haycock, Gianluca Severi, Neil Murphy, Niki L Dimou

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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.

Original language	English
Pages (from-to)	722-736
Number of pages	15
Journal	Cancer Epidemiology, Biomarkers and Prevention
Volume	34
Issue number	5
Early online date	19 Mar 2025
DOIs	https://doi.org/10.1158/1055-9965.EPI-24-0970
Publication status	Published - 1 May 2025

Bibliographical note

Publisher Copyright:
© 2025 The Authors.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1158/1055-9965.EPI-24-0970Licence: CC BY-NC-ND

Handle.net

Persistent link

8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival
Martin, R. M. (Principal Investigator)
1/10/20 → 30/09/25
Project: Research

Cite this

Alduhayh, S., Laskar, R. S., Jiang, X., Zhu, Z., Vincent, E. E., Constantinescu, A., Buchanan, D. D., Grant, R. C., Phipps, A. I., Brenner, H., Huang, W.-Y., Kweon, S.-S., Li, L., Pearlman, R., Castellví-Bel, S., Gruber, S. B., Li, C. I., Pellatt, A. J., Platz, E. A., ... Dimou, N. L. (2025). Association of Genetic Liability to Allergic Diseases with Overall and Early-Onset Colorectal Cancer Risk: a Mendelian randomization study. Cancer Epidemiology, Biomarkers and Prevention, 34(5), 722-736. https://doi.org/10.1158/1055-9965.EPI-24-0970

@article{ecf1fa16b2ee4169ad2aafc54d82840d,

title = "Association of Genetic Liability to Allergic Diseases with Overall and Early-Onset Colorectal Cancer Risk: a Mendelian randomization study",

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.",

author = "Saleh Alduhayh and Laskar, {Ruhina Shirin} and Xia Jiang and Zhaozhong Zhu and Vincent, {Emma E} and Andrei Constantinescu and Buchanan, {Daniel D.} and Grant, {Robert C} and Phipps, {Amanda I.} and Hermann Brenner and Wen-Yi Huang and Sun-Seog Kweon and Li Li and Rachel Pearlman and Sergi Castellv{\'i}-Bel and Gruber, {Stephen B.} and Li, {Christopher I.} and Pellatt, {Andrew J} and Platz, {Elizabeth A.} and {Van Guelpen}, Bethany and Wei Zheng and Chan, {Andrew T.} and Figueiredo, {Jane C.} and Shuji Ogino and Ulrich, {Cornelia M} and Gunter, {Marc J.} and Haycock, {Philip C} and Gianluca Severi and Neil Murphy and Dimou, {Niki L}",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors.",

year = "2025",

month = may,

day = "1",

doi = "10.1158/1055-9965.EPI-24-0970",

language = "English",

volume = "34",

pages = "722--736",

journal = "Cancer Epidemiology, Biomarkers and Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research Inc.",

number = "5",

}

Alduhayh, S, Laskar, RS, Jiang, X, Zhu, Z, Vincent, EE, Constantinescu, A, Buchanan, DD, Grant, RC, Phipps, AI, Brenner, H, Huang, W-Y, Kweon, S-S, Li, L, Pearlman, R, Castellví-Bel, S, Gruber, SB, Li, CI, Pellatt, AJ, Platz, EA, Van Guelpen, B, Zheng, W, Chan, AT, Figueiredo, JC, Ogino, S, Ulrich, CM, Gunter , MJ, Haycock, PC, Severi, G, Murphy, N & Dimou, NL 2025, 'Association of Genetic Liability to Allergic Diseases with Overall and Early-Onset Colorectal Cancer Risk: a Mendelian randomization study', Cancer Epidemiology, Biomarkers and Prevention, vol. 34, no. 5, pp. 722-736. https://doi.org/10.1158/1055-9965.EPI-24-0970

Association of Genetic Liability to Allergic Diseases with Overall and Early-Onset Colorectal Cancer Risk: a Mendelian randomization study. / Alduhayh, Saleh; Laskar, Ruhina Shirin; Jiang, Xia et al.
In: Cancer Epidemiology, Biomarkers and Prevention, Vol. 34, No. 5, 01.05.2025, p. 722-736.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Association of Genetic Liability to Allergic Diseases with Overall and Early-Onset Colorectal Cancer Risk

T2 - a Mendelian randomization study

AU - Alduhayh, Saleh

AU - Laskar, Ruhina Shirin

AU - Jiang, Xia

AU - Zhu, Zhaozhong

AU - Vincent, Emma E

AU - Constantinescu, Andrei

AU - Buchanan, Daniel D.

AU - Grant, Robert C

AU - Phipps, Amanda I.

AU - Brenner, Hermann

AU - Huang, Wen-Yi

AU - Kweon, Sun-Seog

AU - Li, Li

AU - Pearlman, Rachel

AU - Castellví-Bel, Sergi

AU - Gruber, Stephen B.

AU - Li, Christopher I.

AU - Pellatt, Andrew J

AU - Platz, Elizabeth A.

AU - Van Guelpen, Bethany

AU - Zheng, Wei

AU - Chan, Andrew T.

AU - Figueiredo, Jane C.

AU - Ogino, Shuji

AU - Ulrich, Cornelia M

AU - Gunter , Marc J.

AU - Haycock, Philip C

AU - Severi, Gianluca

AU - Murphy, Neil

AU - Dimou, Niki L

PY - 2025/5/1

Y1 - 2025/5/1

N2 - 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.

AB - 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.

U2 - 10.1158/1055-9965.EPI-24-0970

DO - 10.1158/1055-9965.EPI-24-0970

M3 - Article (Academic Journal)

C2 - 39982694

SN - 1055-9965

VL - 34

SP - 722

EP - 736

JO - Cancer Epidemiology, Biomarkers and Prevention

JF - Cancer Epidemiology, Biomarkers and Prevention

IS - 5

ER -

Association of Genetic Liability to Allergic Diseases with Overall and Early-Onset Colorectal Cancer Risk: a Mendelian randomization study

Abstract

Bibliographical note

UN SDGs

Access to Document

Handle.net

Fingerprint

Projects

8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival

Cite this