title: 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.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
authors.forename: Krasimira
authors.initials: K
authors.lastname: Aleksandrova
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Mazda
authors.initials: M
authors.lastname: Jenab
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Eugene
authors.initials: E
authors.lastname: Jansen
authors.forename: Fränzel J B
authors.initials: FJ
authors.lastname: van Duijnhoven
authors.forename: Sabina
authors.initials: S
authors.lastname: Rinaldi
authors.forename: Veronika
authors.initials: V
authors.lastname: Fedirko
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunter
authors.forename: Sabine
authors.initials: S
authors.lastname: Westphal
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Jytte
authors.initials: J
authors.lastname: Halkjær
authors.forename: Antoine
authors.initials: A
authors.lastname: Racine
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Annekatrin
authors.initials: A
authors.lastname: Lukanova
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Pagona
authors.initials: P
authors.lastname: Lagiou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Amalia
authors.initials: A
authors.lastname: Mattiello
authors.forename: Valeria
authors.initials: V
authors.lastname: Pala
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Genevieve
authors.initials: G
authors.lastname: Buckland
authors.forename: María-José
authors.initials: MJ
authors.lastname: Sánchez
authors.forename: Pilar
authors.initials: P
authors.lastname: Amiano
authors.forename: José María
authors.initials: JM
authors.lastname: Huerta
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.forename: Virginia
authors.initials: V
authors.lastname: Menéndez
authors.forename: Petra H
authors.initials: PH
authors.lastname: Peeters
authors.forename: Stefan
authors.initials: S
authors.lastname: Söderberg
authors.forename: Richard
authors.initials: R
authors.lastname: Palmqvist
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Allen
authors.forename: Francesca L
authors.initials: FL
authors.lastname: Crowe
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Nickolas
authors.initials: N
authors.lastname: Wareham
authors.forename: Tobias
authors.initials: T
authors.lastname: Pischon
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000503:physiopathology*; D005060:Europe; D005260:Female; D006801:Humans; D020738:Leptin / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D011446:Prospective Studies; D054411:Receptors, Leptin / Q000502:physiology*
chemical_list: D020738:Leptin; D054411:Receptors, Leptin