Leptin and soluble leptin receptor in risk of colorectal cancer in the European prospective investigation into cancer and nutrition cohort

Krasimira Aleksandrova, Heiner Boeing, Mazda Jenab, H. Bas Bueno-de-Mesquita, Eugene Jansen, Fränzel J B Van Duijnhoven, Sabina Rinaldi, Veronika Fedirko, Isabelle Romieu, Elio Riboli, Marc J. Gunter, Sabine Westphal, Kim Overvad, Anne Tjnøneland, Jytte Halkjræ, Antoine Racine, Marie Christine Boutron-Ruault, Françoise Clavel-Chapelon, Rudolf Kaaks, Annekatrin LukanovaAntonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Amalia Mattiello, Valeria Pala, Domenico Palli, Rosario Tumino, Paolo Vineis, Genevieve Buckland, María Jośe Śanchez, Pilar Amiano, José María Huerta, Aurelio Barricarte, Virginia Meneńdez, Petra H. Peeters, Stefan Sod̈erberg, Richard Palmqvist, Naomi E. Allen, Francesca L. Crowe, Kay Tee Khaw, Nickolas Wareham, Tobias Pischon

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Leptin, a peptide hormone produced primarily by the adipocytes, is hypothesized to play a role in the pathogenesis of colorectal cancer (CRC). Soluble leptin receptor (sOB-R) may regulate leptin's physiologic functions; however its relation to CRC risk is unknown. This study explored the association of leptin and sOB-R with risk of CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 1,129 incident CRC cases (713 colon, 416 rectal) were matched within risk sets to 1,129 controls. Conditional logistic regression was used to calculate relative risks (RR) and 95% confidence intervals (CI). After multivariable adjustment including body mass index (BMI), waist circumference, and baseline leptin concentrations, sOB-R was strongly inversely associated with CRC (RR comparing the highest quintile vs. the lowest, 0.55; 95% CI, 0.40-0.76; Ptrend = 0.0004) and colon cancer (RR, 0.42; 95% CI, 0.28-0.63, Ptrend = 0.0001); whereas no association was seen for rectal cancer (RR adjusted for BMI and waist circumference, 0.83; 95% CI, 0.48-1.44, P trend = 0.38). In contrast, leptin was not associated with risk of CRC (RR adjusted for BMI and waist circumference, 0.85; 95% CI, 0.56-1.29, Ptrend = 0.23). Additional adjustments for circulating metabolic biomarkers did not attenuate these results. These novel findings suggest a strong inverse association between circulating sOB-R and CRC risk, independent of obesity measures, leptin concentrations, and other metabolic biomarkers. Further research is needed to confirm the potentially important role of sOB-R in CRC pathogenesis.

Original languageEnglish
Pages (from-to)5328-5337
Number of pages10
JournalCancer Research
Volume72
Issue number20
DOIs
Publication statusPublished - Oct 15 2012

Fingerprint

Leptin Receptors
Leptin
Colorectal Neoplasms
Neoplasms
Confidence Intervals
Waist Circumference
Body Mass Index
Biomarkers
Peptide Hormones
Rectal Neoplasms
Adipocytes
Colonic Neoplasms
Case-Control Studies
Colon
Obesity
Logistic Models

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Aleksandrova, K., Boeing, H., Jenab, M., Bueno-de-Mesquita, H. B., Jansen, E., Van Duijnhoven, F. J. B., ... Pischon, T. (2012). Leptin and soluble leptin receptor in risk of colorectal cancer in the European prospective investigation into cancer and nutrition cohort. Cancer Research, 72(20), 5328-5337. https://doi.org/10.1158/0008-5472.CAN-12-0465

Leptin and soluble leptin receptor in risk of colorectal cancer in the European prospective investigation into cancer and nutrition cohort. / Aleksandrova, Krasimira; Boeing, Heiner; Jenab, Mazda; Bueno-de-Mesquita, H. Bas; Jansen, Eugene; Van Duijnhoven, Fränzel J B; Rinaldi, Sabina; Fedirko, Veronika; Romieu, Isabelle; Riboli, Elio; Gunter, Marc J.; Westphal, Sabine; Overvad, Kim; Tjnøneland, Anne; Halkjræ, Jytte; Racine, Antoine; Boutron-Ruault, Marie Christine; Clavel-Chapelon, Françoise; Kaaks, Rudolf; Lukanova, Annekatrin; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Mattiello, Amalia; Pala, Valeria; Palli, Domenico; Tumino, Rosario; Vineis, Paolo; Buckland, Genevieve; Śanchez, María Jośe; Amiano, Pilar; Huerta, José María; Barricarte, Aurelio; Meneńdez, Virginia; Peeters, Petra H.; Sod̈erberg, Stefan; Palmqvist, Richard; Allen, Naomi E.; Crowe, Francesca L.; Khaw, Kay Tee; Wareham, Nickolas; Pischon, Tobias.

In: Cancer Research, Vol. 72, No. 20, 15.10.2012, p. 5328-5337.

Research output: Contribution to journalArticle

Aleksandrova, K, Boeing, H, Jenab, M, Bueno-de-Mesquita, HB, Jansen, E, Van Duijnhoven, FJB, Rinaldi, S, Fedirko, V, Romieu, I, Riboli, E, Gunter, MJ, Westphal, S, Overvad, K, Tjnøneland, A, Halkjræ, J, Racine, A, Boutron-Ruault, MC, Clavel-Chapelon, F, Kaaks, R, Lukanova, A, Trichopoulou, A, Lagiou, P, Trichopoulos, D, Mattiello, A, Pala, V, Palli, D, Tumino, R, Vineis, P, Buckland, G, Śanchez, MJ, Amiano, P, Huerta, JM, Barricarte, A, Meneńdez, V, Peeters, PH, Sod̈erberg, S, Palmqvist, R, Allen, NE, Crowe, FL, Khaw, KT, Wareham, N & Pischon, T 2012, 'Leptin and soluble leptin receptor in risk of colorectal cancer in the European prospective investigation into cancer and nutrition cohort', Cancer Research, vol. 72, no. 20, pp. 5328-5337. https://doi.org/10.1158/0008-5472.CAN-12-0465
Aleksandrova, Krasimira ; Boeing, Heiner ; Jenab, Mazda ; Bueno-de-Mesquita, H. Bas ; Jansen, Eugene ; Van Duijnhoven, Fränzel J B ; Rinaldi, Sabina ; Fedirko, Veronika ; Romieu, Isabelle ; Riboli, Elio ; Gunter, Marc J. ; Westphal, Sabine ; Overvad, Kim ; Tjnøneland, Anne ; Halkjræ, Jytte ; Racine, Antoine ; Boutron-Ruault, Marie Christine ; Clavel-Chapelon, Françoise ; Kaaks, Rudolf ; Lukanova, Annekatrin ; Trichopoulou, Antonia ; Lagiou, Pagona ; Trichopoulos, Dimitrios ; Mattiello, Amalia ; Pala, Valeria ; Palli, Domenico ; Tumino, Rosario ; Vineis, Paolo ; Buckland, Genevieve ; Śanchez, María Jośe ; Amiano, Pilar ; Huerta, José María ; Barricarte, Aurelio ; Meneńdez, Virginia ; Peeters, Petra H. ; Sod̈erberg, Stefan ; Palmqvist, Richard ; Allen, Naomi E. ; Crowe, Francesca L. ; Khaw, Kay Tee ; Wareham, Nickolas ; Pischon, Tobias. / Leptin and soluble leptin receptor in risk of colorectal cancer in the European prospective investigation into cancer and nutrition cohort. In: Cancer Research. 2012 ; Vol. 72, No. 20. pp. 5328-5337.
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T1 - Leptin and soluble leptin receptor in risk of colorectal cancer in the European prospective investigation into cancer and nutrition cohort

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 - Rinaldi, Sabina

AU - Fedirko, Veronika

AU - Romieu, Isabelle

AU - Riboli, Elio

AU - Gunter, Marc J.

AU - Westphal, Sabine

AU - Overvad, Kim

AU - Tjnøneland, Anne

AU - Halkjræ, Jytte

AU - Racine, Antoine

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 - Mattiello, Amalia

AU - Pala, Valeria

AU - Palli, Domenico

AU - Tumino, Rosario

AU - Vineis, Paolo

AU - Buckland, Genevieve

AU - Śanchez, María Jośe

AU - Amiano, Pilar

AU - Huerta, José María

AU - Barricarte, Aurelio

AU - Meneńdez, Virginia

AU - Peeters, Petra H.

AU - Sod̈erberg, Stefan

AU - Palmqvist, Richard

AU - Allen, Naomi E.

AU - Crowe, Francesca L.

AU - Khaw, Kay Tee

AU - Wareham, Nickolas

AU - Pischon, Tobias

PY - 2012/10/15

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N2 - Leptin, a peptide hormone produced primarily by the adipocytes, is hypothesized to play a role in the pathogenesis of colorectal cancer (CRC). Soluble leptin receptor (sOB-R) may regulate leptin's physiologic functions; however its relation to CRC risk is unknown. This study explored the association of leptin and sOB-R with risk of CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 1,129 incident CRC cases (713 colon, 416 rectal) were matched within risk sets to 1,129 controls. Conditional logistic regression was used to calculate relative risks (RR) and 95% confidence intervals (CI). After multivariable adjustment including body mass index (BMI), waist circumference, and baseline leptin concentrations, sOB-R was strongly inversely associated with CRC (RR comparing the highest quintile vs. the lowest, 0.55; 95% CI, 0.40-0.76; Ptrend = 0.0004) and colon cancer (RR, 0.42; 95% CI, 0.28-0.63, Ptrend = 0.0001); whereas no association was seen for rectal cancer (RR adjusted for BMI and waist circumference, 0.83; 95% CI, 0.48-1.44, P trend = 0.38). In contrast, leptin was not associated with risk of CRC (RR adjusted for BMI and waist circumference, 0.85; 95% CI, 0.56-1.29, Ptrend = 0.23). Additional adjustments for circulating metabolic biomarkers did not attenuate these results. These novel findings suggest a strong inverse association between circulating sOB-R and CRC risk, independent of obesity measures, leptin concentrations, and other metabolic biomarkers. Further research is needed to confirm the potentially important role of sOB-R in CRC pathogenesis.

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