TY - JOUR
T1 - Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries
T2 - A Multinational Cohort Study
AU - Murphy, Neil
AU - Ward, Heather A.
AU - Jenab, Mazda
AU - Rothwell, Joseph A.
AU - Boutron-Ruault, Marie Christine
AU - Carbonnel, Franck
AU - Kvaskoff, Marina
AU - Kaaks, Rudolf
AU - Kühn, Tilman
AU - Boeing, Heiner
AU - Aleksandrova, Krasimira
AU - Weiderpass, Elisabete
AU - Skeie, Guri
AU - Borch, Kristin Benjaminsen
AU - Tjønneland, Anne
AU - Kyrø, Cecilie
AU - Overvad, Kim
AU - Dahm, Christina C.
AU - Jakszyn, Paula
AU - Sánchez, Maria Jose
AU - Gil, Leire
AU - Huerta, José M.
AU - Barricarte, Aurelio
AU - Quirós, J. Ramón
AU - Khaw, Kay Tee
AU - Wareham, Nick
AU - Bradbury, Kathryn E.
AU - Trichopoulou, Antonia
AU - La Vecchia, Carlo
AU - Karakatsani, Anna
AU - Palli, Domenico
AU - Grioni, Sara
AU - Tumino, Rosario
AU - Fasanelli, Francesca
AU - Panico, Salvatore
AU - Bueno-de-Mesquita, Bas
AU - Peeters, Petra H.
AU - Gylling, Björn
AU - Myte, Robin
AU - Jirström, Karin
AU - Berntsson, Jonna
AU - Xue, Xiaonan
AU - Riboli, Elio
AU - Cross, Amanda J.
AU - Gunter, Marc J.
N1 - Funding Information:
Funding The coordination of the European Prospective Investigation into Cancer and Nutrition (EPIC) is supported financially by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (France); German Cancer Aid, German Cancer Research Center (German Cancer Research Center), Federal Ministry of Education and Research (Federal Ministry of Education and Research), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (Ministry of Health, Welfare and Sport), Netherlands Cancer Registry (Netherlands Cancer Registry), LK Research Funds, Dutch Prevention Funds, Dutch Zorg Onderzoek Nederland, World Cancer Research Fund, Statistics Netherlands (The Netherlands); Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund (Health Research Fund), PI13/00061 to Granada; PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), and Navarra, Instituto de Salud Carlos III Cooperative Research in Health (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk, C570/A16491 and C8221/A19170 to EPIC-Oxford), and the Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). For information on how to submit an application for gaining access to EPIC data and/or biospecimens, please follow the instructions at http://epic.iarc.fr/access/index.php.
Publisher Copyright:
© 2019 AGA Institute
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - 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.
AB - 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.
KW - Anatomic Subsite
KW - Colorectal Cancer
KW - Distal Colon
KW - Heterogeneity
KW - Proximal Colon
KW - Rectum
KW - Risk Factors
UR - https://www.scopus.com/pages/publications/85065866885
U2 - 10.1016/j.cgh.2018.07.030
DO - 10.1016/j.cgh.2018.07.030
M3 - Article
C2 - 30056182
AN - SCOPUS:85065866885
SN - 1542-3565
VL - 17
SP - 1323-1331.e6
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 7
ER -