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)

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 dis...

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Published in:	PLoS medicine 2016-04, Vol.13 (4), p.e1001988-e1001988
Main Authors:	Murphy, Neil, Cross, Amanda J, Abubakar, Mustapha, Jenab, Mazda, Aleksandrova, Krasimira, Boutron-Ruault, Marie-Christine, Dossus, Laure, Racine, Antoine, Kühn, Tilman, Katzke, Verena A, Tjønneland, Anne, Petersen, Kristina E N, Overvad, Kim, Quirós, J Ramón, Jakszyn, Paula, Molina-Montes, Esther, Dorronsoro, Miren, Huerta, José-María, Barricarte, Aurelio, Khaw, Kay-Tee, Wareham, Nick, Travis, Ruth C, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrios, Masala, Giovanna, Krogh, Vittorio, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Bueno-de-Mesquita, H Bas, Siersema, Peter D, Peeters, Petra H, Ohlsson, Bodil, Ericson, Ulrika, Palmqvist, Richard, Nyström, Hanna, Weiderpass, Elisabete, Skeie, Guri, Freisling, Heinz, Kong, So Yeon, Tsilidis, Kostas, Muller, David C, Riboli, Elio, Gunter, Marc J
Format:	Article
Language:	eng
Subjects:	Adiposity Biology and Life Sciences Biomarkers - blood Body fat Body Mass Index Body Size C-Peptide - blood Cancer and Oncology Cancer och onkologi Cancer therapies Cardiovascular disease Case-Control Studies Chi-Square Distribution Clinical Medicine Colorectal cancer Colorectal Neoplasms - diagnosis Colorectal Neoplasms - epidemiology Community medicine, Social medicine: 801 Complications and side effects Diabetes Europe - epidemiology Female Genetic aspects Genotype & phenotype Health sciences: 800 Health Status Helsefag: 800 Humans Hyperinsulinism - blood Hyperinsulinism - diagnosis Hyperinsulinism - epidemiology Incidence Insulin Investigations Klinisk medicin Logistic Models Male Medical and Health Sciences Medical disciplines: 700 Medicin och hälsovetenskap Medicine and Health Sciences Medisinske Fag: 700 Metabolism Middle Aged Multivariate Analysis Nutrition research Obesity Obesity - blood Obesity - diagnosis Obesity - epidemiology Obesity, Metabolically Benign - blood Obesity, Metabolically Benign - diagnosis Obesity, Metabolically Benign - epidemiology Odds Ratio Peptides Phenotype Phenotypes Prospective Studies Protective Factors Researchers Risk Assessment Risk Factors Samfunnsmedisin, sosialmedisin: 801 Studies VDP Waist Circumference Weight control
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Summary:	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. 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
ISSN:	1549-1676 1549-1277 1549-1676