Heterogeneity of colorectal cancer risk factors by anatomical subsite in 10 European countries: a multinational cohort study

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Title: Heterogeneity of colorectal cancer risk factors by anatomical subsite in 10 European countries: a multinational cohort study
Authors: Murphy, N
Ward, HA
Jenab, M
Rothwell, JA
Boutron-Ruault, M-C
Carbonnel, F
Kvaskoff, M
Kaaks, R
Kuhn, T
Boeing, H
Aleksandrova, K
Weiderpass, E
Skeie, G
Borch, KB
Tjønneland, A
Kyrø, C
Overvad, K
Dahm, CC
Jakszyn, P
Sanchez, M-JS
Gil, L
Huerta, JM
Barricarte, A
Quiros, JR
Khaw, K-T
Wareham, N
Bradbury, KE
Trichopoulou, A
La Vecchia, C
Karakatsani, A
Palli, D
Grioni, S
Tumino, R
Fasanelli, F
Panico, S
Bueno-de-Mesquita, B
Peeters, PH
Gylling, B
Myte, R
Jirstrom, K
Berntsson, J
Xue, X
Riboli, E
Cross, AJ
Gunter, MJ
Item Type: Journal Article
Abstract: Background and 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 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 14.9 years (median) follow-up of 521,330 men and women, 6,291 colorectal cancer cases occurred. Physical activity was inversely related to proximal colon and distal colon cancer, but not to rectal cancer (P-heterogeneity=0.03). Height was positively associated with proximal and distal colon cancer only, but not rectal cancer (P-heterogeneity=0.0001). For men, but not women, heterogeneous relationships were observed for body mass index (P-heterogeneity=0.008) and waist circumference (P-heterogeneity=0.03), with weaker positive associations found for rectal cancer, compared to 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=0.05). No heterogeneity by anatomical site was found for alcohol consumption, diabetes, nonsteroidal anti-inflammatory drug use, and reproductive/menstrual factors. Conclusions The physical activity, anthropometry, and smoking relationships with colorectal cancer risk differed by subsite, supporting the hypothesis that tumors in different anatomical regions may have distinct etiologies.
Issue Date: Jun-2019
Date of Acceptance: 25-Jul-2018
URI: http://hdl.handle.net/10044/1/62329
DOI: https://doi.org/10.1016/j.cgh.2018.07.030
ISSN: 1542-3565
Publisher: Elsevier
Start Page: 1323
End Page: 1331.e6
Journal / Book Title: Clinical Gastroenterology and Hepatology
Volume: 17
Issue: 7
Copyright Statement: © 2019 by the AGA Institute. Published by Elsevier, Inc. This is an openaccess article under the CC BY IGO license (http://creativecommons.org/licenses/by/3.0/igo/).
Sponsor/Funder: Imperial College Trust
Funder's Grant Number: P47328
Keywords: Science & Technology
Life Sciences & Biomedicine
Gastroenterology & Hepatology
Colorectal Cancer
Risk Factors
Anatomic Subsite
Proximal Colon
Distal Colon
Anatomic Subsite
Colorectal Cancer
Distal Colon
Proximal Colon
Risk Factors
1103 Clinical Sciences
Gastroenterology & Hepatology
Publication Status: Published
Online Publication Date: 2018-07-26
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care

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