Association of Genetic Liability to Allergic Diseases with Overall and Early-Onset Colorectal Cancer Risk: A Mendelian Randomization Study.

Authors

Alduhayh S, Laskar RS, Jiang X, Zhu Z, Vincent EE, Constantinescu AE, Buchanan DD, Grant RC, Phipps AI, Brenner H, Huang WY, Kweon SS, Li L, Pearlman R, Castellví-Bel S, Gruber SB, Li CI, Pellatt A, Platz EA, Van Guelpen B, ...show more Zheng W, Chan AT, Figueiredo JC, Ogino S, Ulrich CM, Gunter MJ, Haycock P, Severi G, Murphy N, Dimou N

Affiliations

• Public Health Department, College of Public Health, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
• Department of Oncology, Early Cancer Institute, University of Cambridge, Cambridge, United Kingdom.
• Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
• Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
• MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom.
• Colorectal Oncogenomics Group, Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Parkville, Australia.
• Division of Medical Oncology and Haematology, Princess Margaret Cancer Center, University Health Network, Toronto, Canada.
• Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington.
• Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
• Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Abstract

BACKGROUND: The 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 the risk of overall and early-onset colorectal cancer.

METHODS: Genome-wide association study summary statistical data were used to identify genetic variants associated with allergic diseases (Nvariants = 65) and individual allergic conditions (asthma, hay fever/allergic rhinitis, and 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 {OR per log (odds) = 0.90 [95% confidence interval (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, whereas 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.