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).

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dc.creatorMurphy, Neil
dc.creatorCross, Amanda J
dc.creatorAbubakar, Mustapha
dc.creatorJenab, Mazda
dc.creatorAleksandrova, Krasimira
dc.creatorBoutron-Ruault, Marie-Christine
dc.creatorDossus, Laure
dc.creatorRacine, Antoine
dc.creatorKühn, Tilman
dc.creatorKatzke, Verena A
dc.creatorTjønneland, Anne
dc.creatorPetersen, Kristina EN
dc.creatorOvervad, Kim
dc.creatorQuirós, J Ramón
dc.creatorJakszyn, Paula
dc.creatorMolina-Montes, Esther
dc.creatorDorronsoro, Miren
dc.creatorHuerta, José-María
dc.creatorBarricarte, Aurelio
dc.creatorKhaw, Kay-Tee
dc.creatorWareham, Nick
dc.creatorTravis, Ruth C
dc.creatorTrichopoulou, Antonia
dc.creatorLagiou, Pagona
dc.creatorTrichopoulos, Dimitrios
dc.creatorMasala, Giovanna
dc.creatorKrogh, Vittorio
dc.creatorTumino, Rosario
dc.creatorVineis, Paolo
dc.creatorPanico, Salvatore
dc.creatorBueno-de-Mesquita, H Bas
dc.creatorSiersema, Peter D
dc.creatorPeeters, Petra H
dc.creatorOhlsson, Bodil
dc.creatorEricson, Ulrika
dc.creatorPalmqvist, Richard
dc.creatorNyström, Hanna
dc.creatorWeiderpass, Elisabete
dc.creatorSkeie, Guri
dc.creatorFreisling, Heinz
dc.creatorKong, So Yeon
dc.creatorTsilidis, Kostas
dc.creatorMuller, David C
dc.creatorRiboli, Elio
dc.creatorGunter, Marc J
dc.date2018-11-09T00:30:13Z
dc.date2018-11-09T00:30:13Z
dc.date2016-04
dc.date.accessioned2026-08-03T03:42:20Z
dc.descriptionBACKGROUND: 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. METHODS AND FINDINGS: 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 ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥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 regression 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 metabolically 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 possible 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 pattern of associations was observed. CONCLUSIONS: 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 parameters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer.
dc.formatElectronic-eCollection
dc.formatapplication/pdf
dc.identifier1549-1277
dc.identifierhttps://www.repository.cam.ac.uk/handle/1810/284871
dc.identifier10.17863/CAM.32244
dc.identifier1549-1676
dc.identifier.urihttps://repo.dare.co.zw/handle/123456789/179663
dc.languageeng
dc.languageeng
dc.publisherPublic Library of Science (PLoS)
dc.publisherhttps://doi.org/10.1371/journal.pmed.1001988
dc.rightsAttribution 4.0 International
dc.rightshttps://creativecommons.org/licenses/by/4.0/
dc.subjectAdiposity
dc.subjectBiomarkers
dc.subjectBody Mass Index
dc.subjectBody Size
dc.subjectC-Peptide
dc.subjectCase-Control Studies
dc.subjectChi-Square Distribution
dc.subjectColorectal Neoplasms
dc.subjectEurope
dc.subjectFemale
dc.subjectHealth Status
dc.subjectHumans
dc.subjectHyperinsulinism
dc.subjectIncidence
dc.subjectLogistic Models
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectMultivariate Analysis
dc.subjectObesity
dc.subjectObesity, Metabolically Benign
dc.subjectOdds Ratio
dc.subjectPhenotype
dc.subjectProspective Studies
dc.subjectProtective Factors
dc.subjectRisk Assessment
dc.subjectRisk Factors
dc.subjectWaist Circumference
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).
dc.typeArticle

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