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

Neil Murphy, Heather A. Ward, Mazda Jenab, Joseph A. Rothwell, Marie Christine Boutron-Ruault, Franck Carbonnel, Marina Kvaskoff, Rudolf Kaaks, Tilman Kühn, Heiner Boeing, Krasimira Aleksandrova, Elisabete Weiderpass, Guri Skeie, Kristin Benjaminsen Borch, Anne Tjønneland, Cecilie Kyrø, Kim Overvad, Christina C. Dahm, Paula Jakszyn, Maria Jose SánchezLeire Gil, José M. Huerta, Aurelio Barricarte, J. Ramón Quirós, Kay Tee Khaw, Nick Wareham, Kathryn E. Bradbury, Antonia Trichopoulou, Carlo La Vecchia, Anna Karakatsani, Domenico Palli, Sara Grioni, Rosario Tumino, Francesca Fasanelli, Salvatore Panico, Bas Bueno-de-Mesquita, Petra H. Peeters, Björn Gylling, Robin Myte, Karin Jirström, Jonna Berntsson, Xiaonan (Nan) Xue, Elio Riboli, Amanda J. Cross, Marc J. Gunter

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1323-1331.e6
JournalClinical Gastroenterology and Hepatology
Volume17
Issue number7
DOIs
StatePublished - Jun 1 2019

Fingerprint

Colonic Neoplasms
Colorectal Neoplasms
Cohort Studies
Rectal Neoplasms
Colon
Smoking
Exercise
Neoplasms
Anthropometry
Waist Circumference
Proportional Hazards Models
Rectum
Alcohol Drinking
Life Style
Body Mass Index
Anti-Inflammatory Agents
Joints
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Murphy, N., Ward, H. A., Jenab, M., Rothwell, J. A., Boutron-Ruault, M. C., Carbonnel, F., ... Gunter, M. J. (2019). Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries: A Multinational Cohort Study. Clinical Gastroenterology and Hepatology, 17(7), 1323-1331.e6. https://doi.org/10.1016/j.cgh.2018.07.030

Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries : A Multinational Cohort Study. / Murphy, Neil; Ward, Heather A.; Jenab, Mazda; Rothwell, Joseph A.; Boutron-Ruault, Marie Christine; Carbonnel, Franck; Kvaskoff, Marina; Kaaks, Rudolf; Kühn, Tilman; Boeing, Heiner; Aleksandrova, Krasimira; Weiderpass, Elisabete; Skeie, Guri; Borch, Kristin Benjaminsen; Tjønneland, Anne; Kyrø, Cecilie; Overvad, Kim; Dahm, Christina C.; Jakszyn, Paula; Sánchez, Maria Jose; Gil, Leire; Huerta, José M.; Barricarte, Aurelio; Quirós, J. Ramón; Khaw, Kay Tee; Wareham, Nick; Bradbury, Kathryn E.; Trichopoulou, Antonia; La Vecchia, Carlo; Karakatsani, Anna; Palli, Domenico; Grioni, Sara; Tumino, Rosario; Fasanelli, Francesca; Panico, Salvatore; Bueno-de-Mesquita, Bas; Peeters, Petra H.; Gylling, Björn; Myte, Robin; Jirström, Karin; Berntsson, Jonna; Xue, Xiaonan (Nan); Riboli, Elio; Cross, Amanda J.; Gunter, Marc J.

In: Clinical Gastroenterology and Hepatology, Vol. 17, No. 7, 01.06.2019, p. 1323-1331.e6.

Research output: Contribution to journalArticle

Murphy, N, Ward, HA, Jenab, M, Rothwell, JA, Boutron-Ruault, MC, Carbonnel, F, Kvaskoff, M, Kaaks, R, Kühn, T, Boeing, H, Aleksandrova, K, Weiderpass, E, Skeie, G, Borch, KB, Tjønneland, A, Kyrø, C, Overvad, K, Dahm, CC, Jakszyn, P, Sánchez, MJ, Gil, L, Huerta, JM, Barricarte, A, Quirós, JR, Khaw, KT, 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, Jirström, K, Berntsson, J, Xue, XN, Riboli, E, Cross, AJ & Gunter, MJ 2019, 'Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries: A Multinational Cohort Study', Clinical Gastroenterology and Hepatology, vol. 17, no. 7, pp. 1323-1331.e6. https://doi.org/10.1016/j.cgh.2018.07.030
Murphy, Neil ; Ward, Heather A. ; Jenab, Mazda ; Rothwell, Joseph A. ; Boutron-Ruault, Marie Christine ; Carbonnel, Franck ; Kvaskoff, Marina ; Kaaks, Rudolf ; Kühn, Tilman ; Boeing, Heiner ; Aleksandrova, Krasimira ; Weiderpass, Elisabete ; Skeie, Guri ; Borch, Kristin Benjaminsen ; Tjønneland, Anne ; Kyrø, Cecilie ; Overvad, Kim ; Dahm, Christina C. ; Jakszyn, Paula ; Sánchez, Maria Jose ; Gil, Leire ; Huerta, José M. ; Barricarte, Aurelio ; Quirós, J. Ramón ; Khaw, Kay Tee ; Wareham, Nick ; Bradbury, Kathryn E. ; Trichopoulou, Antonia ; La Vecchia, Carlo ; Karakatsani, Anna ; Palli, Domenico ; Grioni, Sara ; Tumino, Rosario ; Fasanelli, Francesca ; Panico, Salvatore ; Bueno-de-Mesquita, Bas ; Peeters, Petra H. ; Gylling, Björn ; Myte, Robin ; Jirström, Karin ; Berntsson, Jonna ; Xue, Xiaonan (Nan) ; Riboli, Elio ; Cross, Amanda J. ; Gunter, Marc J. / Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries : A Multinational Cohort Study. In: Clinical Gastroenterology and Hepatology. 2019 ; Vol. 17, No. 7. pp. 1323-1331.e6.
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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.",
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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 (Nan)

AU - Riboli, Elio

AU - Cross, Amanda J.

AU - Gunter, Marc J.

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

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