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Ulrika Ericson

Ulrika Ericson

Associate professor

Ulrika Ericson

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)

Author

  • Neil Murphy
  • Amanda J Cross
  • Mustapha Abubakar
  • Mazda Jenab
  • Krasimira Aleksandrova
  • Marie-Christine Boutron-Ruault
  • Laure Dossus
  • Antoine Racine
  • Tilman Kühn
  • Verena A Katzke
  • Anne Tjønneland
  • Kristina E N Petersen
  • Kim Overvad
  • J Ramón Quirós
  • Paula Jakszyn
  • Esther Molina-Montes
  • Miren Dorronsoro
  • José-María Huerta
  • Aurelio Barricarte
  • Kay-Tee Khaw
  • Nick Wareham
  • Ruth C Travis
  • Antonia Trichopoulou
  • Pagona Lagiou
  • Dimitrios Trichopoulos
  • Giovanna Masala
  • Vittorio Krogh
  • Rosario Tumino
  • Paolo Vineis
  • Salvatore Panico
  • H Bas Bueno-de-Mesquita
  • Peter D Siersema
  • Petra H Peeters
  • Bodil Ohlsson
  • Ulrika Ericson
  • Richard Palmqvist
  • Hanna Nyström
  • Elisabete Weiderpass
  • Guri Skeie
  • Heinz Freisling
  • So Yeon Kong
  • Kostas Tsilidis
  • David C Muller
  • Elio Riboli
  • Marc J Gunter

Summary, in English

BACKGROUND: 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.

Department/s

  • Internal Medicine - Epidemiology
  • Diabetes - Cardiovascular Disease
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2016

Language

English

Publication/Series

PLoS Medicine

Volume

13

Issue

4

Document type

Journal article

Publisher

Public Library of Science

Topic

  • Cancer and Oncology

Status

Published

Research group

  • Internal Medicine - Epidemiology
  • Diabetes - Cardiovascular Disease

ISBN/ISSN/Other

  • ISSN: 1549-1676