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)

• 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: English
• 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
• ISSN: 1549-1676; 1549-1277; 1549-1676
• DOI: 10.1371/journal.pmed.1001988

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