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

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机构： [1]Public Health Department, College of Public Health, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. [2]Department of Oncology, Early Cancer Institute, University of Cambridge, Cambridge, United Kingdom. [3]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. [4]Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China. [5]Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Solna, Sweden. [6]Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. [7]MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom. [8]Bristol Medical School, Population Health Sciences, University of Bristol, Bristol, United Kingdom. [9]School of Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom. [10]Colorectal Oncogenomics Group, Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Parkville, Australia. [11]University of Melbourne Centre for Cancer Research, The University of Melbourne, Parkville, Australia. [12]Genomic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, Australia. [13]Division of Medical Oncology and Haematology, Princess Margaret Cancer Center, University Health Network, Toronto, Canada. [14]Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington. [15]Department of Epidemiology, University of Washington, Seattle, Washington. [16]Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. [17]Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. [18]Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. [19]Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Korea. [20]Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, Korea. [21]Department of Family Medicine, University of Virginia, Charlottesville, Virginia. [22]Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio. [23]Gastroenterology Department, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain. [24]Center for Precision Medicine and Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, California. [25]Department of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas. [26]Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. [27]Department of Diagnostics and Intervention, Oncology, Umea University, Umea, Sweden. [28]Wallenberg Centre for Molecular Medicine, Umea University, Umea, Sweden. [29]Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee. [30]Massachusetts General Hospital, Clinical and Translational Epidemiology Unit, Boston, Massachusetts. [31]Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California. [32]Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts. [33]Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. [34]Broad Institute of MIT and Harvard, Cambridge, Massachusetts. [35]Tokyo Medical and Dental University (Institute of Science Tokyo), Tokyo, Japan. [36]Department of Population Health Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah. [37]Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France. [38]Cancer Epidemiology and Prevention Research Unit, School of Public Health, Imperial College London, London, United Kingdom. [39]Universite Paris-Saclay, UVSQ, Univ. Paris-Sud, Gustave Roussy, Inserm, U1018, Exposome, Heredity, Cancer, and Health Team, CESP, Villejuif, France.

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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.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.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].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.©2025 The Authors; Published by the American Association for Cancer Research.

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出版当年[2025]版：

大类 | 2 区医学

小类 | 2 区公共卫生、环境卫生与职业卫生 3 区肿瘤学

最新[2025]版：

大类 | 2 区医学

小类 | 2 区公共卫生、环境卫生与职业卫生 3 区肿瘤学

第一作者：

第一作者机构： [1]Public Health Department, College of Public Health, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

通讯作者：

通讯机构： [7]MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom. [8]Bristol Medical School, Population Health Sciences, University of Bristol, Bristol, United Kingdom. [9]School of Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.

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