Adiposity, mediating biomarkers and risk of colon cancer in the European prospective investigation into cancer and nutrition study

Krasimira Aleksandrova, Dagmar Drogan, Heiner Boeing, Mazda Jenab, H. Bas Bueno-De-Mesquita, Eugene Jansen, Fränzel J B Van Duijnhoven, Sabina Rinaldi, Veronika Fedirko, Isabelle Romieu, Rudolf Kaaks, Elio Riboli, Marc J. Gunter, Dora Romaguera, Sabine Westhpal, Kim Overvad, Anne Tjønneland, Jytte Halkjær, Marie Christine Boutron-Ruault, Françoise Clavel-ChapelonAnnekatrin Lukanova, Antonia Trichopoulou, Dimitrios Trichopoulos, Pavlos Vidalis, Salvatore Panico, Claudia Agnoli, Domenico Palli, Rosario Tumino, Paolo Vineis, Genevieve Buckland, José Juan Sánchez-Cruz, Miren Dorronsoro, María José Tormo Díaz, Aurelio Barricarte, J. Ramon Quiros, Petra H. Peeters, Anne M. May, Göran Hallmans, Richard Palmqvist, Francesca L. Crowe, Kay Tee Khaw, Nickolas Wareham, Tobias Pischon

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer in men and women. We analyzed data from a prospective nested case-control study among 662 incident colon cancer cases matched within risk sets to 662 controls. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. The percent effect change and corresponding CIs were estimated after adjusting for biomarkers shown to be associated with colon cancer risk. After multivariable adjustment, WC was associated with colon cancer risk in men (top vs. bottom tertile RR 1.68, 95% CI 1.06-2.65; p trend = 0.02) and in women (RR 1.67, 95% CI 1.09-2.56; p trend = 0.03). BMI was associated with risk only in men. The association of WC with colon cancer was accounted mostly for by three biomarkers, high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin and soluble leptin receptor, which in combination explained 46% (95% CI 37-57%) of the association in men and 50% (95% CI 40-65%) of the association in women. Similar results were observed for the associations with BMI in men. These data suggest that alterations in levels of these metabolic biomarkers may represent a primary mechanism of action in the relation of adiposity with colon cancer. Further studies are warranted to determine whether altering their concentrations may reduce colon cancer risk.

Original languageEnglish
Pages (from-to)612-621
Number of pages10
JournalInternational Journal of Cancer
Volume134
Issue number3
DOIs
Publication statusPublished - 2013

Fingerprint

Adiposity
Colonic Neoplasms
Biomarkers
Confidence Intervals
Neoplasms
Waist Circumference
Body Mass Index
Leptin Receptors
Adiponectin
HDL Cholesterol
Case-Control Studies
Molecular Weight
Logistic Models

Keywords

  • adiposity
  • body mass index
  • colon cancer
  • mediating biomarkers
  • waist circumference

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Aleksandrova, K., Drogan, D., Boeing, H., Jenab, M., Bas Bueno-De-Mesquita, H., Jansen, E., ... Pischon, T. (2013). Adiposity, mediating biomarkers and risk of colon cancer in the European prospective investigation into cancer and nutrition study. International Journal of Cancer, 134(3), 612-621. https://doi.org/10.1002/ijc.28368

Adiposity, mediating biomarkers and risk of colon cancer in the European prospective investigation into cancer and nutrition study. / Aleksandrova, Krasimira; Drogan, Dagmar; Boeing, Heiner; Jenab, Mazda; Bas Bueno-De-Mesquita, H.; Jansen, Eugene; Van Duijnhoven, Fränzel J B; Rinaldi, Sabina; Fedirko, Veronika; Romieu, Isabelle; Kaaks, Rudolf; Riboli, Elio; Gunter, Marc J.; Romaguera, Dora; Westhpal, Sabine; Overvad, Kim; Tjønneland, Anne; Halkjær, Jytte; Boutron-Ruault, Marie Christine; Clavel-Chapelon, Françoise; Lukanova, Annekatrin; Trichopoulou, Antonia; Trichopoulos, Dimitrios; Vidalis, Pavlos; Panico, Salvatore; Agnoli, Claudia; Palli, Domenico; Tumino, Rosario; Vineis, Paolo; Buckland, Genevieve; Sánchez-Cruz, José Juan; Dorronsoro, Miren; Díaz, María José Tormo; Barricarte, Aurelio; Ramon Quiros, J.; Peeters, Petra H.; May, Anne M.; Hallmans, Göran; Palmqvist, Richard; Crowe, Francesca L.; Khaw, Kay Tee; Wareham, Nickolas; Pischon, Tobias.

In: International Journal of Cancer, Vol. 134, No. 3, 2013, p. 612-621.

Research output: Contribution to journalArticle

Aleksandrova, K, Drogan, D, Boeing, H, Jenab, M, Bas Bueno-De-Mesquita, H, Jansen, E, Van Duijnhoven, FJB, Rinaldi, S, Fedirko, V, Romieu, I, Kaaks, R, Riboli, E, Gunter, MJ, Romaguera, D, Westhpal, S, Overvad, K, Tjønneland, A, Halkjær, J, Boutron-Ruault, MC, Clavel-Chapelon, F, Lukanova, A, Trichopoulou, A, Trichopoulos, D, Vidalis, P, Panico, S, Agnoli, C, Palli, D, Tumino, R, Vineis, P, Buckland, G, Sánchez-Cruz, JJ, Dorronsoro, M, Díaz, MJT, Barricarte, A, Ramon Quiros, J, Peeters, PH, May, AM, Hallmans, G, Palmqvist, R, Crowe, FL, Khaw, KT, Wareham, N & Pischon, T 2013, 'Adiposity, mediating biomarkers and risk of colon cancer in the European prospective investigation into cancer and nutrition study', International Journal of Cancer, vol. 134, no. 3, pp. 612-621. https://doi.org/10.1002/ijc.28368
Aleksandrova, Krasimira ; Drogan, Dagmar ; Boeing, Heiner ; Jenab, Mazda ; Bas Bueno-De-Mesquita, H. ; Jansen, Eugene ; Van Duijnhoven, Fränzel J B ; Rinaldi, Sabina ; Fedirko, Veronika ; Romieu, Isabelle ; Kaaks, Rudolf ; Riboli, Elio ; Gunter, Marc J. ; Romaguera, Dora ; Westhpal, Sabine ; Overvad, Kim ; Tjønneland, Anne ; Halkjær, Jytte ; Boutron-Ruault, Marie Christine ; Clavel-Chapelon, Françoise ; Lukanova, Annekatrin ; Trichopoulou, Antonia ; Trichopoulos, Dimitrios ; Vidalis, Pavlos ; Panico, Salvatore ; Agnoli, Claudia ; Palli, Domenico ; Tumino, Rosario ; Vineis, Paolo ; Buckland, Genevieve ; Sánchez-Cruz, José Juan ; Dorronsoro, Miren ; Díaz, María José Tormo ; Barricarte, Aurelio ; Ramon Quiros, J. ; Peeters, Petra H. ; May, Anne M. ; Hallmans, Göran ; Palmqvist, Richard ; Crowe, Francesca L. ; Khaw, Kay Tee ; Wareham, Nickolas ; Pischon, Tobias. / Adiposity, mediating biomarkers and risk of colon cancer in the European prospective investigation into cancer and nutrition study. In: International Journal of Cancer. 2013 ; Vol. 134, No. 3. pp. 612-621.
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AU - Aleksandrova, Krasimira

AU - Drogan, Dagmar

AU - Boeing, Heiner

AU - Jenab, Mazda

AU - Bas Bueno-De-Mesquita, H.

AU - Jansen, Eugene

AU - Van Duijnhoven, Fränzel J B

AU - Rinaldi, Sabina

AU - Fedirko, Veronika

AU - Romieu, Isabelle

AU - Kaaks, Rudolf

AU - Riboli, Elio

AU - Gunter, Marc J.

AU - Romaguera, Dora

AU - Westhpal, Sabine

AU - Overvad, Kim

AU - Tjønneland, Anne

AU - Halkjær, Jytte

AU - Boutron-Ruault, Marie Christine

AU - Clavel-Chapelon, Françoise

AU - Lukanova, Annekatrin

AU - Trichopoulou, Antonia

AU - Trichopoulos, Dimitrios

AU - Vidalis, Pavlos

AU - Panico, Salvatore

AU - Agnoli, Claudia

AU - Palli, Domenico

AU - Tumino, Rosario

AU - Vineis, Paolo

AU - Buckland, Genevieve

AU - Sánchez-Cruz, José Juan

AU - Dorronsoro, Miren

AU - Díaz, María José Tormo

AU - Barricarte, Aurelio

AU - Ramon Quiros, J.

AU - Peeters, Petra H.

AU - May, Anne M.

AU - Hallmans, Göran

AU - Palmqvist, Richard

AU - Crowe, Francesca L.

AU - Khaw, Kay Tee

AU - Wareham, Nickolas

AU - Pischon, Tobias

PY - 2013

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N2 - Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer in men and women. We analyzed data from a prospective nested case-control study among 662 incident colon cancer cases matched within risk sets to 662 controls. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. The percent effect change and corresponding CIs were estimated after adjusting for biomarkers shown to be associated with colon cancer risk. After multivariable adjustment, WC was associated with colon cancer risk in men (top vs. bottom tertile RR 1.68, 95% CI 1.06-2.65; p trend = 0.02) and in women (RR 1.67, 95% CI 1.09-2.56; p trend = 0.03). BMI was associated with risk only in men. The association of WC with colon cancer was accounted mostly for by three biomarkers, high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin and soluble leptin receptor, which in combination explained 46% (95% CI 37-57%) of the association in men and 50% (95% CI 40-65%) of the association in women. Similar results were observed for the associations with BMI in men. These data suggest that alterations in levels of these metabolic biomarkers may represent a primary mechanism of action in the relation of adiposity with colon cancer. Further studies are warranted to determine whether altering their concentrations may reduce colon cancer risk.

AB - Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer in men and women. We analyzed data from a prospective nested case-control study among 662 incident colon cancer cases matched within risk sets to 662 controls. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. The percent effect change and corresponding CIs were estimated after adjusting for biomarkers shown to be associated with colon cancer risk. After multivariable adjustment, WC was associated with colon cancer risk in men (top vs. bottom tertile RR 1.68, 95% CI 1.06-2.65; p trend = 0.02) and in women (RR 1.67, 95% CI 1.09-2.56; p trend = 0.03). BMI was associated with risk only in men. The association of WC with colon cancer was accounted mostly for by three biomarkers, high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin and soluble leptin receptor, which in combination explained 46% (95% CI 37-57%) of the association in men and 50% (95% CI 40-65%) of the association in women. Similar results were observed for the associations with BMI in men. These data suggest that alterations in levels of these metabolic biomarkers may represent a primary mechanism of action in the relation of adiposity with colon cancer. Further studies are warranted to determine whether altering their concentrations may reduce colon cancer risk.

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KW - colon cancer

KW - mediating biomarkers

KW - waist circumference

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