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dc.contributor.authorMurphy, Neil
dc.contributor.authorCross, Amanda J
dc.contributor.authorAbubakar, Mustapha
dc.contributor.authorJenab, Mazda
dc.contributor.authorAleksandrova, Krasmira
dc.contributor.authorBoutron-Ruault, Marie-Christine
dc.contributor.authorDossus, Laure
dc.contributor.authorRacine, Antoine
dc.contributor.authorKühn, Tilman
dc.contributor.authorKatzke, Verena A.
dc.contributor.authorTjønneland, Anne
dc.contributor.authorPetersen, Kristina E N
dc.contributor.authorOvervad, Kim
dc.contributor.authorQuiros, J Ramon
dc.contributor.authorJakszyn, Paula
dc.contributor.authorMolina-Montes, Esther
dc.contributor.authorDorronsoro, Miren
dc.contributor.authorHuerta, José-Maria
dc.contributor.authorBarricarte, Aurelio
dc.contributor.authorKhaw, Kay-Tee
dc.contributor.authorWareham, Nick
dc.contributor.authorTravis, Ruth C
dc.contributor.authorTrichopoulou, Antonia
dc.contributor.authorLagiou, Pagona
dc.contributor.authorTrichopoulos, Dimitrios
dc.contributor.authorMasala, Giovanna
dc.contributor.authorKrogh, Vittorio
dc.contributor.authorTumino, Rosario
dc.contributor.authorVineis, Paolo
dc.contributor.authorPanico, Salvatore
dc.contributor.authorBueno-de-Mesquita, H. Bas
dc.contributor.authorSiersema, Peter D
dc.contributor.authorPeeters, Petra H
dc.contributor.authorOhlsson, Bodil
dc.contributor.authorEricson, Ulrika
dc.contributor.authorPalmqvist, Richard
dc.contributor.authorNyström, Hanna
dc.contributor.authorWeiderpass, Elisabete
dc.contributor.authorSkeie, Guri
dc.contributor.authorFreisling, Heinz
dc.contributor.authorKong, So Yeon
dc.contributor.authorTsilidis, Kostas
dc.contributor.authorMuller, David C
dc.contributor.authorRiboli, Eilo
dc.contributor.authorGunter, Marc J
dc.date.accessioned2017-02-22T14:24:06Z
dc.date.available2017-02-22T14:24:06Z
dc.date.issued2016-04-05
dc.description.abstractBackground:<br> Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown.<br>Methods and Findings:<br> The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI 2' 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI 2' 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [2'80 cm for women and 2'94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of <0.05 was considered statistically significant. In multivariable-adjusted conditional logistic regres- sion models with BMI used to define adiposity, compared with metabolically healthy/normal weight individuals, we observed a higher colorectal cancer risk among metabolically unhealthy/normal weight (odds ratio [OR] = 1.59, 95% CI 1.10–2.28) and metabolically unhealthy/overweight (OR = 1.40, 95% CI 1.01–1.94) participants, but not among metaboli- cally healthy/overweight individuals (OR = 0.96, 95% CI 0.65–1.42). Among the overweight individuals, lower colorectal cancer risk was observed for metabolically healthy/overweight individuals compared with metabolically unhealthy/overweight individuals (OR = 0.69, 95% CI 0.49–0.96). These associations were generally consistent when waist circumference was used as the measure of adiposity. To our knowledge, there is no universally accepted clinical definition for using C-peptide level as an indication of hyperinsulinaemia. Therefore, a possi- ble limitation of our analysis was that the classification of individuals as being hyperinsulinaemic—based on their C-peptide level—was arbitrary. However, when we used quartiles or the median of C-peptide, instead of tertiles, as the cut-point of hyperinsulinaemia, a similar pat- tern of associations was observed.<br> Conclusions:<br> These results support the idea that individuals with the metabolically healthy/overweight phenotype (with normal insulin levels) are at lower colorectal cancer risk than those with hyperinsulinaemia. The combination of anthropometric measures with metabolic parame- ters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer.en_US
dc.description.sponsorshipThe coordination of EPIC is financially supported by the European Commission (DGSANCO); and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer; Institut Gustave Roussy; Mutuelle Générale de l’Education Nationale; and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum; and Federal Ministry of Education and Research (Germany); Hellenic Health Foundation; Stavros Niarchos Foundation; and the Hellenic Ministry of Health and Social Solidarity (Greece); Italian Association for Research on Cancer (AIRC); National Research Council; and Associazione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS) Ragusa, Associazione Volontari Italiani Sangu (AVIS) Ragusa, Sicilian Government (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); and Statistics Netherlands (the Netherlands); European Research Council (ERC) (grant number ERC-2009-AdG 232997) and Nordforsk; and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS); Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra; and the Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública and Instituto de Salud Carlos II (ISCIII RETIC) (RD06/ 0020) (Spain); Swedish Cancer Society; Swedish Scientific Council; and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK; Medical Research Council; Stroke Association; British Heart Foundation; Department of Health; Food Standards Agency; Wellcome Trust (UK); and National Cancer Institute (USA) (grant number: 1RO1CA102460) (PI, Professor Rudolf Kaaks). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.descriptionSource: <a href=http://dx.doi.org/10.1371/journal.pmed.1001988>doi: 10.1371/journal.pmed.1001988</a>en_US
dc.identifier.citationMurphy N, Cross AJ, Abubakar M, Jenab M, Aleksandrova K, Boutron-Ruault M-C, et al. (2016) A Nested Case–Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). PLoS Med 13(4): e1001988. doi:10.1371/journal. pmed.1001988en_US
dc.identifier.cristinIDFRIDAID 1365379
dc.identifier.doi10.1371/journal.pmed.1001988
dc.identifier.issn1549-1277
dc.identifier.issn1549-1676
dc.identifier.urihttps://hdl.handle.net/10037/10342
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.journalPLoS Medicine
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801en_US
dc.subjectVDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801en_US
dc.titleA Nested Case–Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)en_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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