Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00-1.17, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, p = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.

Bill Lyons Informatics Centre UCL Cancer Institute University College London London United Kingdom

Cancer Control Research BC Cancer Vancouver BC Canada

Cancer Epidemiology and Intelligence Division Cancer Council Victoria Melbourne VIC Australia

Cancer Epidemiology Research Programme Catalan Institute of Oncology IDIBELL L'Hospitalet de Llobregat Barcelona Spain

Cancer Epidemiology Unit University of Oxford Oxford United Kingdom

Carolina Center for Genome Sciences University of North Carolina at Chapel Hill Chapel Hill NC United States

Center for Chronic Immunodeficiency University Medical Center Freiburg Freiburg im Breisgau Germany

Center for Gerontology and Healthcare Research Brown University School of Public Health Providence RI United States

Centre for Big Data Research in Health University of New South Wales Sydney NSW Australia

Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health University of Melbourne Melbourne VIC Australia

Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston MA United States

CIBER de Epidemiología y Salud Pública Barcelona Spain

Clinical Genetics Service Department of Medicine Memorial Sloan Kettering Cancer Center New York NY United States

CPO Piemonte and Unit of Medical Statistics and Epidemiology Department Translational Medicine University of Piemonte Orientale Novara Italy

Department of Biomedical Physiology and Kinesiology Simon Fraser University Burnaby BC Canada

Department of Biostatistics Bloomberg School of Public Health Johns Hopkins University Baltimore MD United States

Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute and MF MU Brno Czechia

Department of Computational Biology St Jude Children's Research Hospital Memphis TN United States

Department of Environmental Health Sciences Yale School of Public Health New Haven CT United States

Department of Environmental Medicine New York University School of Medicine New York NY United States

Department of Epidemiology and Biostatistics University of California San Francisco San Francisco CA United States

Department of Epidemiology Brown School of Public Health Providence RI United States

Department of Epidemiology Harvard School of Public Health Boston MA United States

Department of Epidemiology University of North Carolina at Chapel Hill Chapel Hill NC United States

Department of Family Medicine and Public Health Sciences Wayne State University Detroit MI United States

Department of Health Sciences Research Mayo Clinic Rochester MN United States

Department of Health Sciences University of York York United Kingdom

Department of Health Services Policy and Practice Brown University School of Public Health Providence RI United States

Department of Hematology and Medical Oncology Emory University School of Medicine Atlanta GA United States

Department of Hematology Centre Léon Bérard Lyon France

Department of Hematology Hospices Civils de Lyon Lyon France

Department of Hematology Université Lyon 1 Lyon France

Department of Immunology Genetics and Pathology Uppsala University Uppsala Sweden

Department of Internal Medicine Carver College of Medicine The University of Iowa Iowa City IA United States

Department of Internal Medicine Huntsman Cancer Institute Salt Lake City UT United States

Department of Internal Medicine University of Utah School of Medicine Salt Lake City UT United States

Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden

Department of Medicine Solna Karolinska Institutet Stockholm Sweden

Department of Medicine Stanford University School of Medicine Stanford CA United States

Department of Obstetrics and Gynecology New York University School of Medicine New York NY United States

Department of Oncology School of Medicine Johns Hopkins University Baltimore MD United States

Department of Pathology AP HP Necker Enfants malades Université Paris Descartes Sorbonne Paris Cité Paris France

Department of Preventive Medicine USC Keck School of Medicine University of Southern California Los Angeles CA United States

Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MD United States

Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany

Division of Endocrinology Diabetes and Metabolism The Ohio State University Columbus OH United States

Division of Environmental Epidemiology Institute for Risk Assessment Sciences Utrecht University Utrecht Netherlands

Division of General Internal Medicine Mayo Clinic College of Medicine and Science Rochester MN United States

Division of Health Surveillance and Research Department of Epidemiology Research Statens Serum Institut Copenhagen Denmark

Division of Hematology and Hematologic Malignancies Department of Internal Medicine and Huntsman Cancer Institute University of Utah School of Medicine Salt Lake City UT United States

Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle WA United States

Environmental and Occupational Epidemiology Unit Oncological Network Prevention and Research Institute Florence Italy

Epidemiology of Childhood and Adolescent Cancers Group Inserm Center of Research in Epidemiology and Statistics Sorbonne Paris Cité Paris France

Epidemiology Research Program American Cancer Society Atlanta GA United States

Equipe Experimental and Clinical Models of Lymphomagenesis Cancer Research Center of Lyon Institut National de Santé et de la Recherche Médicale UMR1052 Pierre Benite Lyon France

Genetic Epidemiology Laboratory Department of Pathology University of Melbourne Melbourne VIC Australia

Genome Sciences Centre BC Cancer Vancouver BC Canada

Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany

Hematology Center Karolinska University Hospital Stockholm Sweden

INSERM U1052 Cancer Research Center of Lyon Centre Léon Bérard Lyon France

INSERM U1231 Registre des Hémopathies Malignes de Côte d'Or University of Burgundy and Dijon University Hospital Dijon France

Interdisciplinary Department of Medicine University of Bari Bari Italy

International Agency for Research on Cancer Lyon France

International Agency for Research on Cancer World Health Organization Lyon France

Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht Netherlands

Laboratory of Translational Genomics Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MD United States

Norris Comprehensive Cancer Center USC Keck School of Medicine University of Southern California Los Angeles CA United States

Ontario Health Study Toronto ON Canada

Perlmutter Cancer Center NYU Langone Medical Center New York NY United States

Regional Cancer Prevention Laboratory Oncological Network Prevention and Research Institute Florence Italy

Registre des hémopathies malignes de la Gironde Institut Bergonié Bordeaux France

School of Nursing and Human Sciences Dublin City University Dublin Ireland

School of Population and Public Health University of British Columbia Vancouver BC Canada

School of Public Health Imperial College London London United Kingdom

The Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York NY United States

Université Paris Descartes Paris France

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