Περίληψη:
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. Cancer Res; 72(20); 5328-37. (C) 2012 AACR.
Συγγραφείς:
Aleksandrova, Krasimira
Boeing, Heiner
Jenab, Mazda and
Bueno-de-Mesquita, H. Bas
Jansen, Eugene
van Duijnhoven, Franzel
J. B.
Rinaldi, Sabina
Fedirko, Veronika
Romieu, Isabelle and
Riboli, Elio
Gunter, Marc J.
Westphal, Sabine
Overvad, Kim
and Tjonneland, Anne
Halkjaer, Jytte
Racine, Antoine and
Boutron-Ruault, Marie-Christine
Clavel-Chapelon, Francoise and
Kaaks, Rudolf
Lukanova, Annekatrin
Trichopoulou, Antonia and
Lagiou, Pagona
Trichopoulos, Dimitrios
Mattiello, Amalia and
Pala, Valeria
Palli, Domenico
Tumino, Rosario
Vineis, Paolo
and Buckland, Genevieve
Sanchez, Maria-Jose
Amiano, Pilar and
Maria Huerta, Jose
Barricarte, Aurelio
Menendez, Virginia and
Peeters, Petra H.
Soderberg, Stefan
Palmqvist, Richard and
Allen, Naomi E.
Crowe, Francesca L.
Khaw, Kay-Tee
Wareham,
Nickolas
Pischon, Tobias
