Leptin and Soluble Leptin Receptor in Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition Cohort

被引：55

作者：

Aleksandrova, Krasimira ^{[1
]}

Boeing, Heiner ^{[1
]}

Jenab, Mazda ^{[2
]}

Bueno-de-Mesquita, H. Bas ^{[3
,4
]}

Jansen, Eugene ^{[3
]}

van Duijnhoven, Franzel J. B. ^{[3
,6
]}

Rinaldi, Sabina ^{[2
]}

Fedirko, Veronika ^{[2
]}

Romieu, Isabelle ^{[2
]}

Riboli, Elio ^{[7
]}

Gunter, Marc J. ^{[7
]}

Westphal, Sabine ^{[8
]}

Overvad, Kim ^{[9
]}

Tjonneland, Anne ^{[10
]}

Halkjaer, Jytte ^{[10
]}

Racine, Antoine ^{[11
,12
]}

Boutron-Ruault, Marie-Christine ^{[11
,12
]}

Clavel-Chapelon, Francoise ^{[11
,12
]}

Kaaks, Rudolf ^{[13
]}

Lukanova, Annekatrin ^{[13
]}

Trichopoulou, Antonia ^{[14
,15
]}

Lagiou, Pagona ^{[14
,16
,17
]}

Trichopoulos, Dimitrios ^{[16
,17
]}

Mattiello, Amalia ^{[18
]}

Pala, Valeria ^{[19
]}

Palli, Domenico ^{[20
]}

Tumino, Rosario ^{[21
,22
]}

Vineis, Paolo ^{[7
,23
]}

Buckland, Genevieve ^{[24
]}

Sanchez, Maria-Jose ^{[25
,26
]}

Amiano, Pilar ^{[26
,27
]}

Maria Huerta, Jose ^{[26
,28
]}

Barricarte, Aurelio ^{[26
,29
]}

Menendez, Virginia ^{[30
]}

Peeters, Petra H. ^{[5
,7
]}

Soderberg, Stefan ^{[31
]}

Palmqvist, Richard ^{[32
]}

Allen, Naomi E. ^{[33
]}

Crowe, Francesca L. ^{[33
]}

Khaw, Kay-Tee

Wareham, Nickolas

Pischon, Tobias ^{[1
,34
]}

机构：

[1] German Inst Human Nutr Potsdam Rehbrucke, Dept Epidemiol, D-14558 Nuthetal, Germany

[2] Int Agcy Res Canc, F-69372 Lyon, France

[3] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands

[4] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands

[5] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands

[6] Wageningen Univ, Div Human Nutr, Wageningen, Netherlands

[7] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England

[8] Univ Magdeburg, Inst Clin Chem, D-39106 Magdeburg, Germany

[9] Aarhus Univ, Sch Publ Hlth, Dept Epidemiol, Aarhus, Denmark

[10] Diet Genes & Environm Danish Canc Soc Res Ctr, Copenhagen, Denmark

[11] Inst Gustave Roussy, INSERM, Ctr Res Epidemiol & Populat Hlth, F-94805 Villejuif, France

[12] Paris S Univ, UMRS, Villejuif, France

[13] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany

[14] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, WHO Collaborating Ctr Food & Nutr Policies, GR-11527 Athens, Greece

[15] Hellen Hlth Fdn, Athens, Greece

[16] Acad Athens, Bur Epidemiol Res, Athens, Greece

[17] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[18] Univ Naples Federico II, Dept Clin & Expt Med, Naples, Italy

[19] Fdn IRCCS Ist Nazl Tumori, Nutr Epidemiol Unit, Milan, Italy

[20] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy

[21] MP Arezzo Hosp, Canc Registry, Ragusa, Italy

[22] MP Arezzo Hosp, Histopathol Unit, Ragusa, Italy

[23] HuGeF Fdn, Turin, Italy

[24] Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Programme, Unit Nutr Environm & Canc, Barcelona, Spain

[25] Andalusian Sch Publ Hlth, Granada, Spain

[26] CIBER Epidemiol & Salud Publ CIBERESP, Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain

[27] Reg Govt Basque Country, Dept Hlth, BIODonostia Res Inst, Publ Hlth Div Gipuzkoa, San Sebastian, Spain

[28] Murcia Reg Hlth Author, Dept Epidemiol, Murcia, Spain

[29] Navarre Publ Hlth Inst, Pamplona, Spain

[30] Publ Hlth Directorate, Asturias, Spain

[31] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden

[32] Umea Univ, Dept Med Bosci, Umea, Sweden

[33] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England

[34] Max Delbrueck Ctr Mol Med MDC, Mol Epidemiol Grp, Berlin, Germany

来源：

CANCER RESEARCH | 2012年 / 72卷 / 20期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

RECTAL-CANCER; PLASMA LEPTIN; COLON-CANCER; OBESITY; INSULIN; WOMEN; MEN; ADIPONECTIN; EXPRESSION; BIOMARKERS;

D O I：

10.1158/0008-5472.CAN-12-0465

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：5328 / 5337

页数：10

共 50 条

[1]

Aleksandrova K, 2012, FRONT BIOSC IN PRESS

[2] Metabolic Syndrome and Risks of Colon and Rectal Cancer: The European Prospective Investigation into Cancer and Nutrition Study [J].

Aleksandrova, Krasimira ;

Boeing, Heiner ;

Jenab, Mazda ;

Bueno-de-Mesquita, H. Bas ;

Jansen, Eugene ;

van Duijnhoven, Franzel J. B. ;

Fedirko, Veronika ;

Rinaldi, Sabina ;

Romieu, Isabelle ;

Riboli, Elio ;

Romaguera, Dora ;

Overvad, Kim ;

Ostergaard, Jane Nautrup ;

Olsen, Anja ;

Tjonneland, Anne ;

Boutron-Ruault, Marie-Christine ;

Clavel-Chapelon, Francoise ;

Morois, Sophie ;

Masala, Giovanna ;

Agnoli, Claudia ;

Panico, Salvatore ;

Tumino, Rosario ;

Vineis, Paolo ;

Kaaks, Rudolf ;

Lukanova, Annekatrin ;

Trichopoulou, Antonia ;

Naska, Androniki ;

Bamia, Christina ;

Peeters, Petra H. ;

Rodriguez, Laudina ;

Buckland, Genevieve ;

Sanchez, Maria-Jose ;

Dorronsoro, Miren ;

Huerta, Jose-Maria ;

Barricarte, Aurelio ;

Hallmans, Goran ;

Palmqvist, Richard ;

Khaw, Kay-Tee ;

Wareham, Nicholas ;

Allen, Naomi E. ;

Tsilidis, Konstantinos K. ;

Pischon, Tobias .

CANCER PREVENTION RESEARCH, 2011, 4 (11) :1873-1883

[3] Circulating C-Reactive Protein Concentrations and Risks of Colon and Rectal Cancer: A Nested Case-Control Study Within the European Prospective Investigation into Cancer and Nutrition [J].

Aleksandrova, Krasimira ;

Jenab, Mazda ;

Boeing, Heiner ;

Jansen, Eugene ;

Bueno-de-Mesquita, H. Bas ;

Rinaldi, Sabina ;

Riboli, Elio ;

Overvad, Kim ;

Dahm, Christina C. ;

Olsen, Anja ;

Tjonneland, Anne ;

Boutron-Ruault, Marie-Christine ;

Clavel-Chapelon, Francoise ;

Morois, Sophie ;

Palli, Domenico ;

Krogh, Vittorio ;

Tumino, Rosario ;

Vineis, Paolo ;

Panico, Salvatore ;

Kaaks, Rudolf ;

Rohrmann, Sabine ;

Trichopoulou, Antonia ;

Lagiou, Pagona ;

Trichopoulos, Dimitrios ;

van Duijnhoven, Fraenzel J. B. ;

Leufkens, Anke M. ;

Peeters, Petra H. ;

Rodriguez, Laudina ;

Bonet, Catalina ;

Sanchez, Maria-Jose ;

Dorronsoro, Miren ;

Navarro, Carmen ;

Barricarte, Aurelio ;

Palmqvist, Richard ;

Hallmans, Goran ;

Khaw, Kay-Tee ;

Wareham, Nicholas ;

Allen, Naomi E. ;

Spencer, Elizabeth ;

Romaguera, Dora ;

Norat, Teresa ;

Pischon, Tobias .

AMERICAN JOURNAL OF EPIDEMIOLOGY, 2010, 172 (04) :407-418

[4] Leptin stimulates the proliferation of human colon cancer cells in vitro but does not promote the growth of colon cancer xenografts in nude mice or intestinal tumorigenesis in ApcMin/+ mice [J].

Aparicio, T ;

Kotelevets, L ;

Tsocas, A ;

Laigneau, JP ;

Sobhani, I ;

Chastre, E ;

Lehy, T .

GUT, 2005, 54 (08) :1136-1145

[5]

Bell LN, 2006, LEPTIN OBESITY, P33, DOI [10.1007/978-0-387-31416-7_3, DOI 10.1007/978-0-387-31416-7_3]

[6] Regulation of circulating soluble leptin receptor levels by gender, adiposity, sex steroids, and leptin -: Observational and interventional studies in humans [J].

Chan, JL ;

Blüher, S ;

Yiannakouris, N ;

Suchard, MA ;

Kratzsch, J ;

Mantzoros, CS .

DIABETES, 2002, 51 (07) :2105-2112

[7] Leptin concentrations, leptin receptor polymorphisms, and colorectal adenoma risk [J].

Chia, Victoria M. ;

Newcomb, Polly A. ;

Lampe, Johanna W. ;

White, Emily ;

Mandelson, Margaret T. ;

McTiernan, Anne ;

Potter, John D. .

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2007, 16 (12) :2697-2703

[8] Plasma insulin, leptin, and soluble TNF receptors levels in relation to obesity-related atherogenic and thrombogenic cardiovascular disease risk factors among men [J].

Chu, NF ;

Spiegelman, D ;

Hotamisligil, GS ;

Rifai, N ;

Stampfer, M ;

Rimm, EB .

ATHEROSCLEROSIS, 2001, 157 (02) :495-503

[9]

Cinaz P, 2005, J PEDIATR ENDOCR MET, V18, P303

[10] Induction of leptin receptor expression in the liver by leptin and food deprivation [J].

Cohen, P ;

Yang, GQ ;

Yu, XX ;

Soukas, AA ;

Wolfish, CS ;

Friedman, JM ;

Li, C .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (11) :10034-10039

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