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Clin Gastroenterol Hepatol. 2019 Jun;17(7):1323-1331.e6. doi: 10.1016/j.cgh.2018.07.030. Epub 2018 Jul 26.

Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries: A Multinational Cohort Study.

Author information

1
Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France. Electronic address: murphyn@iarc.fr.
2
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
3
Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
4
Le Centre de recherche en Epidémiologie et Santé des Populations, Faculte de Médecine, University Paris-Sud, Faculte de Médecine, Université de Versailles Saint-Quentin-en-Yvelines, INSERM, Université Paris-Saclay, Villejuif, France; Gustave Roussy, Villejuif, France.
5
Le Centre de recherche en Epidémiologie et Santé des Populations, Faculte de Médecine, University Paris-Sud, Faculte de Médecine, Université de Versailles Saint-Quentin-en-Yvelines, INSERM, Université Paris-Saclay, Villejuif, France; Gustave Roussy, Villejuif, France; Department of Gastroenterology, Bicêtre University Hospital, Assistance Publique des Hôpitaux de Paris, Le Kremlin Bicêtre, France.
6
Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
7
Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany.
8
Department of Epidemiology, Nutrition, Immunity and Metabolism Start-up Laboratory, Potsdam-Rehbrücke, Germany.
9
Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Genetic Epidemiology Group, Folkhälsan Research Center and Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
10
Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
11
Danish Cancer Society Research Center, Copenhagen, Denmark.
12
Department of Public Health, Aarhus University, Aarhus, Denmark.
13
Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology, L'Hospitallet de Llobregat, Barcelona, Spain; Facultat de Ciències de la Salut Blanquerna, Universitat Ramon Llull, Barcelona, Spain.
14
Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Madrid, Spain.
15
Public Health Division of Gipuzkoa, Research Institute of BioDonostia, San Sebastian, Spain.
16
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council, Biomedical Research Institute of Murcia-Arrixaca, Murcia, Spain.
17
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; Navarra Institute for Health Research, Pamplona, Spain.
18
Public Health Directorate, Asturias, Spain.
19
University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, United Kingdom.
20
Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
21
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
22
Hellenic Health Foundation, Athens, Greece; World Health Organization Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
23
Hellenic Health Foundation, Athens, Greece; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
24
Hellenic Health Foundation, Athens, Greece; Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Haidari, Greece.
25
Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute, Cancer Research and Prevention Institute, Florence, Italy.
26
Epidemiology and Prevention Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, Milan, Italy.
27
Cancer Registry and Histopathology Department, Civic-M.P. Arezzo Hospital, Azienda Sanitaria Provinciale Ragusa, Italy.
28
Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, Turin, Italy.
29
Dipartimento di Medicina Clinica e Sperimentale, Federico II University, Naples, Italy.
30
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment (Netherlands National Institute for Public Health and the Environment), Bilthoven, The Netherlands; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands; Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
31
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Centre, Utrecht, The Netherlands.
32
Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
33
Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
34
Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.
35
Albert Einstein College of Medicine, Bronx, New York, New York.

Abstract

BACKGROUND & AIMS:

Colorectal cancer located at different anatomical subsites may have distinct etiologies and risk factors. Previous studies that have examined this hypothesis have yielded inconsistent results, possibly because most studies have been of insufficient size to identify heterogeneous associations with precision.

METHODS:

In the European Prospective Investigation into Cancer and Nutrition study, we used multivariable joint Cox proportional hazards models, which accounted for tumors at different anatomical sites (proximal colon, distal colon, and rectum) as competing risks, to examine the relationships between 14 established/suspected lifestyle, anthropometric, and reproductive/menstrual risk factors with colorectal cancer risk. Heterogeneity across sites was tested using Wald tests.

RESULTS:

After a median of 14.9 years of follow-up of 521,330 men and women, 6291 colorectal cancer cases occurred. Physical activity was related inversely to proximal colon and distal colon cancer, but not to rectal cancer (P heterogeneity = .03). Height was associated positively with proximal and distal colon cancer only, but not rectal cancer (P heterogeneity = .0001). For men, but not women, heterogeneous relationships were observed for body mass index (P heterogeneity = .008) and waist circumference (P heterogeneity = .03), with weaker positive associations found for rectal cancer, compared with proximal and distal colon cancer. Current smoking was associated with a greater risk of rectal and proximal colon cancer, but not distal colon cancer (P heterogeneity = .05). No heterogeneity by anatomical site was found for alcohol consumption, diabetes, nonsteroidal anti-inflammatory drug use, and reproductive/menstrual factors.

CONCLUSIONS:

The relationships between physical activity, anthropometry, and smoking with colorectal cancer risk differed by subsite, supporting the hypothesis that tumors in different anatomical regions may have distinct etiologies.

KEYWORDS:

Anatomic Subsite; Colorectal Cancer; Distal Colon; Heterogeneity; Proximal Colon; Rectum; Risk Factors

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