期刊
CANCER RESEARCH
卷 72, 期 20, 页码 5328-5337出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-12-0465
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资金
- World Cancer Research Fund International and Wereld Kanker Onderzoek Fonds (WCRF NL)
- European Commission (DG-SANCO)
- International Agency for Research on Cancer
- Danish Cancer Society (Denmark)
- Ligue contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM
- France)
- Deutsche Krebshilfe, Deutsches Krebsforschungszentrum
- Federal Ministry of Education and Research (Germany)
- Hellenic Health Foundation
- Stavros Niarchos Foundation
- Hellenic Ministry of Health (Greece)
- Italian Association for Research on Cancer (AIRC)
- National Research Council (Italy)
- Dutch Ministry of Public Health, Welfare and Sports (VWS)
- Netherlands Cancer Registry (NKR)
- LK Research Funds
- Dutch Prevention Funds
- Dutch ZON (Zorg Onderzoek Nederland)
- World Cancer Research Fund (WCRF)
- Statistics Netherlands (The Netherlands)
- Nordforsk
- Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway)
- Health Research Fund (FIS)
- Regional Government of Andalucia
- Regional Government of Asturias
- Regional Government of Basque Country
- Regional Government of Murcia
- Regional Government of Navarra
- ISCIII RETIC (Spain) [RD06/0020]
- Swedish Cancer Society
- Swedish Scientific Council
- Regional Government of Skane and Vasterbotten (Sweden)
- Cancer Research UK
- Medical Research Council
- Stroke Association
- British Heart Foundation
- Department of Health, Food Standards Agency
- Wellcome Trust (United Kingdom)
- [ERC-2009-AdG 232997]
- Medical Research Council [G0401527, G0801056B, MC_U106179471, G1000143] Funding Source: researchfish
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.
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