Leptin and soluble leptin receptor in risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition cohort.

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; P(trend) = 0.0004) and colon cancer (RR, 0.42; 95% CI, 0.28-0.63, P(trend) = 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, P(trend) = 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.

• Authors: 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 Tjønneland, Jytte Halkjær, Antoine Racine, Marie-Christine Boutron-Ruault, Françoise Clavel-Chapelon, Rudolf Kaaks, Annekatrin Lukanova, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Amalia Mattiello, Valeria Pala, Domenico Palli, Rosario Tumino, Paolo Vineis, Genevieve Buckland, María-José Sánchez, Pilar Amiano, José María Huerta, Aurelio Barricarte, Virginia Menéndez, Petra H Peeters, Stefan Söderberg, Richard Palmqvist, Naomi E Allen, Francesca L Crowe, Kay-Tee Khaw, Nickolas Wareham, Tobias Pischon
• Journal: Cancer research (Cancer Res) Vol. 72 Issue 20 Pg. 5328-37 (Oct 15 2012) ISSN: 1538-7445 [Electronic] United States
• PMID: 22926557 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Leptin
• Receptors, Leptin

Topics

• Adult
• Aged
• Cohort Studies
• Colorectal Neoplasms (physiopathology)
• Europe
• Female
• Humans
• Leptin (physiology)
• Male
• Middle Aged
• Nutritional Status
• Prospective Studies
• Receptors, Leptin (physiology)