Total and high-molecular weight adiponectin and risk of colorectal cancer: The European prospective investigation into cancer and nutrition study

Krasimira Aleksandrova, Heiner Boeing, Mazda Jenab, H. Bas Bueno-de-Mesquita, Eugene Jansen, Fränzel J B Van duijnhoven, Veronika Fedirko, Sabina Rinaldi, Isabelle Romieu, Elio Riboli, Dora Romaguera, Sabine Westphal, Kim Overvad, Anne Tjønneland, Marie Christine Boutron-Ruault, Françoise Clavel-Chapelon, Rudolf Kaaks, Annekatrin Lukanova, Antonia Trichopoulou, Pagona LagiouDimitrios Trichopoulos, Claudia Agnoli, Amalia Mattiello, Calogero Saieva, Paolo Vineis, Rosario Tumino, Petra H. Peeters, Marcial Argüelles, Catalina Bonet, María José Sánchez, Miren Dorronsoro, Jose María Huerta, Aurelio Barricarte, Richard Palmqvist, Göran Hallmans, Kay Tee Khaw, Nick Wareham, Naomi E. Allen, Francesca L. Crowe, Tobias Pischon

Research output: Contribution to journalArticle

Abstract

Adiponectin-an adipose tissue-derived protein-may provide a molecular link between obesity and colorectal cancer (CRC), but evidence from large prospective studies is limited. In particular, no epidemiological study explored high-molecular weight (HMW) and non-HMW adiponectin fractions in relation to CRC risk, despite them being hypothesized to have differential biological activities, i.e. regulating insulin sensitivity (HMW adiponectin) versus inflammatory response (non-HMW adiponectin). In a prospective, nested case-control study, we investigated whether prediagnostic serum concentrations of total, HMW and non-HMW adiponectin are associated with risk of CRC, independent of obesity and other known CRC risk factors. A total of 1206 incident cases (755 colon and 451 rectal) were matched to 1206 controls using incidence-density sampling. In conditional logistic regression, adjusted for dietary and lifestyle factors, total adiponectin and non-HMW adiponectin concentrations were inversely associated with risk of CRC [relative risk (RR) comparing highest versus lowest quintile = 0.71, 95% confidence interval (CI) = 0.53-0.95, P trend = 0.03 for total adiponectin and RR = 0.45, 95% CI = 0.34-0.61, P trend <0.0001 for non-HMW adiponectin]. HMW adiponectin concentrations were not associated with CRC risk (RR = 0.91, 95% CI = 0.68-1.22, P trend = 0.55). Non-HMW adiponectin was associated with CRC risk even after adjustment for body mass index and waist circumference (RR = 0.39, 95% CI = 0.26-0.60, P trend <0.0001), whereas the association with total adiponectin was no longer significant (RR = 0.81, 95% CI = 0.60-1.09, P trend = 0.23). When stratified by cancer site, non-HMW adiponectin was inversely associated with both colon and rectal cancer. These findings suggest an important role of the relative proportion of non-HMW adiponectin in CRC pathogenesis. Future studies are warranted to confirm these results and to elucidate the underlying mechanisms.

Original languageEnglish
Pages (from-to)1211-1218
Number of pages8
JournalCarcinogenesis
Volume33
Issue number6
DOIs
Publication statusPublished - Nov 2012

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Adiponectin
Colorectal Neoplasms
Molecular Weight
Neoplasms
Confidence Intervals
Obesity
Waist Circumference
Rectal Neoplasms
Colonic Neoplasms
Insulin Resistance
Adipose Tissue
Case-Control Studies
Life Style
Epidemiologic Studies
Colon
Body Mass Index

ASJC Scopus subject areas

  • Cancer Research

Cite this

Aleksandrova, K., Boeing, H., Jenab, M., Bueno-de-Mesquita, H. B., Jansen, E., Van duijnhoven, F. J. B., ... Pischon, T. (2012). Total and high-molecular weight adiponectin and risk of colorectal cancer: The European prospective investigation into cancer and nutrition study. Carcinogenesis, 33(6), 1211-1218. https://doi.org/10.1093/carcin/bgs133

Total and high-molecular weight adiponectin and risk of colorectal cancer : The European prospective investigation into cancer and nutrition study. / Aleksandrova, Krasimira; Boeing, Heiner; Jenab, Mazda; Bueno-de-Mesquita, H. Bas; Jansen, Eugene; Van duijnhoven, Fränzel J B; Fedirko, Veronika; Rinaldi, Sabina; Romieu, Isabelle; Riboli, Elio; Romaguera, Dora; Westphal, Sabine; Overvad, Kim; Tjønneland, Anne; Boutron-Ruault, Marie Christine; Clavel-Chapelon, Françoise; Kaaks, Rudolf; Lukanova, Annekatrin; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Agnoli, Claudia; Mattiello, Amalia; Saieva, Calogero; Vineis, Paolo; Tumino, Rosario; Peeters, Petra H.; Argüelles, Marcial; Bonet, Catalina; Sánchez, María José; Dorronsoro, Miren; Huerta, Jose María; Barricarte, Aurelio; Palmqvist, Richard; Hallmans, Göran; Khaw, Kay Tee; Wareham, Nick; Allen, Naomi E.; Crowe, Francesca L.; Pischon, Tobias.

In: Carcinogenesis, Vol. 33, No. 6, 11.2012, p. 1211-1218.

Research output: Contribution to journalArticle

Aleksandrova, K, Boeing, H, Jenab, M, Bueno-de-Mesquita, HB, Jansen, E, Van duijnhoven, FJB, Fedirko, V, Rinaldi, S, Romieu, I, Riboli, E, Romaguera, D, Westphal, S, Overvad, K, Tjønneland, A, Boutron-Ruault, MC, Clavel-Chapelon, F, Kaaks, R, Lukanova, A, Trichopoulou, A, Lagiou, P, Trichopoulos, D, Agnoli, C, Mattiello, A, Saieva, C, Vineis, P, Tumino, R, Peeters, PH, Argüelles, M, Bonet, C, Sánchez, MJ, Dorronsoro, M, Huerta, JM, Barricarte, A, Palmqvist, R, Hallmans, G, Khaw, KT, Wareham, N, Allen, NE, Crowe, FL & Pischon, T 2012, 'Total and high-molecular weight adiponectin and risk of colorectal cancer: The European prospective investigation into cancer and nutrition study', Carcinogenesis, vol. 33, no. 6, pp. 1211-1218. https://doi.org/10.1093/carcin/bgs133
Aleksandrova, Krasimira ; Boeing, Heiner ; Jenab, Mazda ; Bueno-de-Mesquita, H. Bas ; Jansen, Eugene ; Van duijnhoven, Fränzel J B ; Fedirko, Veronika ; Rinaldi, Sabina ; Romieu, Isabelle ; Riboli, Elio ; Romaguera, Dora ; Westphal, Sabine ; Overvad, Kim ; Tjønneland, Anne ; Boutron-Ruault, Marie Christine ; Clavel-Chapelon, Françoise ; Kaaks, Rudolf ; Lukanova, Annekatrin ; Trichopoulou, Antonia ; Lagiou, Pagona ; Trichopoulos, Dimitrios ; Agnoli, Claudia ; Mattiello, Amalia ; Saieva, Calogero ; Vineis, Paolo ; Tumino, Rosario ; Peeters, Petra H. ; Argüelles, Marcial ; Bonet, Catalina ; Sánchez, María José ; Dorronsoro, Miren ; Huerta, Jose María ; Barricarte, Aurelio ; Palmqvist, Richard ; Hallmans, Göran ; Khaw, Kay Tee ; Wareham, Nick ; Allen, Naomi E. ; Crowe, Francesca L. ; Pischon, Tobias. / Total and high-molecular weight adiponectin and risk of colorectal cancer : The European prospective investigation into cancer and nutrition study. In: Carcinogenesis. 2012 ; Vol. 33, No. 6. pp. 1211-1218.
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T1 - Total and high-molecular weight adiponectin and risk of colorectal cancer

T2 - The European prospective investigation into cancer and nutrition study

AU - Aleksandrova, Krasimira

AU - Boeing, Heiner

AU - Jenab, Mazda

AU - Bueno-de-Mesquita, H. Bas

AU - Jansen, Eugene

AU - Van duijnhoven, Fränzel J B

AU - Fedirko, Veronika

AU - Rinaldi, Sabina

AU - Romieu, Isabelle

AU - Riboli, Elio

AU - Romaguera, Dora

AU - Westphal, Sabine

AU - Overvad, Kim

AU - Tjønneland, Anne

AU - Boutron-Ruault, Marie Christine

AU - Clavel-Chapelon, Françoise

AU - Kaaks, Rudolf

AU - Lukanova, Annekatrin

AU - Trichopoulou, Antonia

AU - Lagiou, Pagona

AU - Trichopoulos, Dimitrios

AU - Agnoli, Claudia

AU - Mattiello, Amalia

AU - Saieva, Calogero

AU - Vineis, Paolo

AU - Tumino, Rosario

AU - Peeters, Petra H.

AU - Argüelles, Marcial

AU - Bonet, Catalina

AU - Sánchez, María José

AU - Dorronsoro, Miren

AU - Huerta, Jose María

AU - Barricarte, Aurelio

AU - Palmqvist, Richard

AU - Hallmans, Göran

AU - Khaw, Kay Tee

AU - Wareham, Nick

AU - Allen, Naomi E.

AU - Crowe, Francesca L.

AU - Pischon, Tobias

PY - 2012/11

Y1 - 2012/11

N2 - Adiponectin-an adipose tissue-derived protein-may provide a molecular link between obesity and colorectal cancer (CRC), but evidence from large prospective studies is limited. In particular, no epidemiological study explored high-molecular weight (HMW) and non-HMW adiponectin fractions in relation to CRC risk, despite them being hypothesized to have differential biological activities, i.e. regulating insulin sensitivity (HMW adiponectin) versus inflammatory response (non-HMW adiponectin). In a prospective, nested case-control study, we investigated whether prediagnostic serum concentrations of total, HMW and non-HMW adiponectin are associated with risk of CRC, independent of obesity and other known CRC risk factors. A total of 1206 incident cases (755 colon and 451 rectal) were matched to 1206 controls using incidence-density sampling. In conditional logistic regression, adjusted for dietary and lifestyle factors, total adiponectin and non-HMW adiponectin concentrations were inversely associated with risk of CRC [relative risk (RR) comparing highest versus lowest quintile = 0.71, 95% confidence interval (CI) = 0.53-0.95, P trend = 0.03 for total adiponectin and RR = 0.45, 95% CI = 0.34-0.61, P trend <0.0001 for non-HMW adiponectin]. HMW adiponectin concentrations were not associated with CRC risk (RR = 0.91, 95% CI = 0.68-1.22, P trend = 0.55). Non-HMW adiponectin was associated with CRC risk even after adjustment for body mass index and waist circumference (RR = 0.39, 95% CI = 0.26-0.60, P trend <0.0001), whereas the association with total adiponectin was no longer significant (RR = 0.81, 95% CI = 0.60-1.09, P trend = 0.23). When stratified by cancer site, non-HMW adiponectin was inversely associated with both colon and rectal cancer. These findings suggest an important role of the relative proportion of non-HMW adiponectin in CRC pathogenesis. Future studies are warranted to confirm these results and to elucidate the underlying mechanisms.

AB - Adiponectin-an adipose tissue-derived protein-may provide a molecular link between obesity and colorectal cancer (CRC), but evidence from large prospective studies is limited. In particular, no epidemiological study explored high-molecular weight (HMW) and non-HMW adiponectin fractions in relation to CRC risk, despite them being hypothesized to have differential biological activities, i.e. regulating insulin sensitivity (HMW adiponectin) versus inflammatory response (non-HMW adiponectin). In a prospective, nested case-control study, we investigated whether prediagnostic serum concentrations of total, HMW and non-HMW adiponectin are associated with risk of CRC, independent of obesity and other known CRC risk factors. A total of 1206 incident cases (755 colon and 451 rectal) were matched to 1206 controls using incidence-density sampling. In conditional logistic regression, adjusted for dietary and lifestyle factors, total adiponectin and non-HMW adiponectin concentrations were inversely associated with risk of CRC [relative risk (RR) comparing highest versus lowest quintile = 0.71, 95% confidence interval (CI) = 0.53-0.95, P trend = 0.03 for total adiponectin and RR = 0.45, 95% CI = 0.34-0.61, P trend <0.0001 for non-HMW adiponectin]. HMW adiponectin concentrations were not associated with CRC risk (RR = 0.91, 95% CI = 0.68-1.22, P trend = 0.55). Non-HMW adiponectin was associated with CRC risk even after adjustment for body mass index and waist circumference (RR = 0.39, 95% CI = 0.26-0.60, P trend <0.0001), whereas the association with total adiponectin was no longer significant (RR = 0.81, 95% CI = 0.60-1.09, P trend = 0.23). When stratified by cancer site, non-HMW adiponectin was inversely associated with both colon and rectal cancer. These findings suggest an important role of the relative proportion of non-HMW adiponectin in CRC pathogenesis. Future studies are warranted to confirm these results and to elucidate the underlying mechanisms.

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