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)

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

doi:10.1371/journal.pmed.1001988

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)

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 KhawNick 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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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

Original language	English
Article number	e1001988
Journal	PLoS Medicine
Volume	13
Issue number	4
DOIs	https://doi.org/10.1371/journal.pmed.1001988
Publication status	Published - 1 Apr 2016

Access to Document

10.1371/journal.pmed.1001988

PhenotypesFinal published version, 224 KB

Cite this

Murphy, N., Cross, A. J., Abubakar, M., Jenab, M., Aleksandrova, K., Boutron-Ruault, M. C., Dossus, L., Racine, A., Kühn, T., Katzke, V. A., Tjønneland, A., Petersen, K. E. N., Overvad, K., Quirós, J. R., Jakszyn, P., Molina-Montes, E., Dorronsoro, M., Huerta, J. M., Barricarte, A., ... Gunter, M. J. (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 Medicine, 13(4), Article e1001988. https://doi.org/10.1371/journal.pmed.1001988

@article{d358c70268e641119640c2f5deecc518,

title = "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)",

abstract = "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 ",

author = "Neil Murphy and Cross, {Amanda J.} and Mustapha Abubakar and Mazda Jenab and Krasimira Aleksandrova and Boutron-Ruault, {Marie Christine} and Laure Dossus and Antoine Racine and Tilman K{\"u}hn and Katzke, {Verena A.} and Anne Tj{\o}nneland and Petersen, {Kristina E N} and Kim Overvad and Quir{\'o}s, {J. Ram{\'o}n} and Paula Jakszyn and Esther Molina-Montes and Miren Dorronsoro and Huerta, {Jos{\'e} Mar{\'i}a} and Aurelio Barricarte and Khaw, {Kay Tee} and Nick Wareham and Travis, {Ruth C.} and Antonia Trichopoulou and Pagona Lagiou and Dimitrios Trichopoulos and Giovanna Masala and Vittorio Krogh and Rosario Tumino and Paolo Vineis and Salvatore Panico and Bueno-de-Mesquita, {H. Bas} and Siersema, {Peter D.} and Peeters, {Petra H.} and Bodil Ohlsson and Ulrika Ericson and Richard Palmqvist and Hanna Nystr{\"o}m and Elisabete Weiderpass and Guri Skeie and Heinz Freisling and Kong, {So Yeon} and Kostas Tsilidis and Muller, {David C.} and Elio Riboli and Gunter, {Marc J.}",

year = "2016",

month = apr,

day = "1",

doi = "10.1371/journal.pmed.1001988",

language = "English",

volume = "13",

journal = "PLoS Medicine",

issn = "1549-1277",

publisher = "Public Library of Science",

number = "4",

}

Murphy, N, Cross, AJ, Abubakar, M, Jenab, M, Aleksandrova, K, Boutron-Ruault, MC, Dossus, L, Racine, A, Kühn, T, Katzke, VA, Tjønneland, A, Petersen, KEN, Overvad, K, Quirós, JR, Jakszyn, P, Molina-Montes, E, Dorronsoro, M, Huerta, JM, Barricarte, A, Khaw, KT, Wareham, N, Travis, RC, Trichopoulou, A, Lagiou, P, Trichopoulos, D, Masala, G, Krogh, V, Tumino, R, Vineis, P, Panico, S, Bueno-de-Mesquita, HB, Siersema, PD, Peeters, PH, Ohlsson, B, Ericson, U, Palmqvist, R, Nyström, H, Weiderpass, E, Skeie, G, Freisling, H, Kong, SY, Tsilidis, K, Muller, DC, Riboli, E & Gunter, MJ 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 Medicine, vol. 13, no. 4, e1001988. https://doi.org/10.1371/journal.pmed.1001988

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). / Murphy, Neil; Cross, Amanda J.; Abubakar, Mustapha et al.
In: PLoS Medicine, Vol. 13, No. 4, e1001988, 01.04.2016.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - 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)

AU - Murphy, Neil

AU - Cross, Amanda J.

AU - Abubakar, Mustapha

AU - Jenab, Mazda

AU - Aleksandrova, Krasimira

AU - Boutron-Ruault, Marie Christine

AU - Dossus, Laure

AU - Racine, Antoine

AU - Kühn, Tilman

AU - Katzke, Verena A.

AU - Tjønneland, Anne

AU - Petersen, Kristina E N

AU - Overvad, Kim

AU - Quirós, J. Ramón

AU - Jakszyn, Paula

AU - Molina-Montes, Esther

AU - Dorronsoro, Miren

AU - Huerta, José María

AU - Barricarte, Aurelio

AU - Khaw, Kay Tee

AU - Wareham, Nick

AU - Travis, Ruth C.

AU - Trichopoulou, Antonia

AU - Lagiou, Pagona

AU - Trichopoulos, Dimitrios

AU - Masala, Giovanna

AU - Krogh, Vittorio

AU - Tumino, Rosario

AU - Vineis, Paolo

AU - Panico, Salvatore

AU - Bueno-de-Mesquita, H. Bas

AU - Siersema, Peter D.

AU - Peeters, Petra H.

AU - Ohlsson, Bodil

AU - Ericson, Ulrika

AU - Palmqvist, Richard

AU - Nyström, Hanna

AU - Weiderpass, Elisabete

AU - Skeie, Guri

AU - Freisling, Heinz

AU - Kong, So Yeon

AU - Tsilidis, Kostas

AU - Muller, David C.

AU - Riboli, Elio

AU - Gunter, Marc J.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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

AB - 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

UR - http://www.scopus.com/inward/record.url?scp=84964777727&partnerID=8YFLogxK

U2 - 10.1371/journal.pmed.1001988

DO - 10.1371/journal.pmed.1001988

M3 - Article

C2 - 27046222

AN - SCOPUS:84964777727

SN - 1549-1277

VL - 13

JO - PLoS Medicine

JF - PLoS Medicine

IS - 4

M1 - e1001988

ER -

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)

Abstract

Access to Document

Other files and links

Fingerprint

Cite this