Metabolic mediators of the association between adult weight gain and colorectal cancer: Data from the european prospective investigation into cancer and nutrition (EPIC) cohort

Krasimira Aleksandrova; Sabrina Schlesinger; Veronika Fedirko; Mazda Jenab; Bas Bueno-De-Mesquita; Heinz Freisling; Isabelle Romieu; Tobias Pischon; Rudolf Kaaks; Marc J. Gunter; Christina C. Dahm; Kim Overvad; Agnetha Linn Rostgaard-Hansen; Anne Tjønneland; Antonia Trichopoulou; Christina Bamia; Pagona Lagiou; Claudia Agnoli; Amalia Mattiello; Kathryn Bradbury; Kay Tee Khaw; Elio Riboli; Heiner Boeing

doi:10.1093/aje/kww194

Metabolic mediators of the association between adult weight gain and colorectal cancer: Data from the european prospective investigation into cancer and nutrition (EPIC) cohort

Krasimira Aleksandrova^*, Sabrina Schlesinger, Veronika Fedirko, Mazda Jenab, Bas Bueno-De-Mesquita, Heinz Freisling, Isabelle Romieu, Tobias Pischon, Rudolf Kaaks, Marc J. Gunter, Christina C. Dahm, Kim Overvad, Agnetha Linn Rostgaard-Hansen, Anne Tjønneland, Antonia Trichopoulou, Christina Bamia, Pagona Lagiou, Claudia Agnoli, Amalia Mattiello, Kathryn BradburyKay Tee Khaw, Elio Riboli, Heiner Boeing

^*Corresponding author for this work

14 Citations (Scopus)

Abstract

Evidence indicates that gaining weight in adult life is associated with an elevated risk of colorectal cancer; however, biological mechanisms that may explain this association remain unclear. We evaluated the mediation effect of 20 different biomarkers on the relationship between adult weight gain and colorectal cancer, using data from a prospective nested case-control study of 452 incident cases diagnosed between 1992 and 2003 and matched within risk sets to 452 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The proportions of mediated effects (%) were estimated on the basis of differences in percent effect changes in conditional logistic regression models with and without additional adjustment for individual biomarkers. Greater adult weight gain (≥300 g/year vs. <300 g/year) was associated with a higher risk of colon cancer (multivariableadjusted relative risk = 1.54, 95% confidence interval: 1.07, 2.24) but not rectal cancer (relative risk = 1.07, 95% confidence interval: 0.68, 1.66). This association was accounted for mostly by attained waist circumference (reduction of 61%) and by the biomarkers soluble leptin receptor (reduction of 43%) and glycated hemoglobin (reduction of 28%). These novel data suggest that the observed association between adult weight gain and colon cancer could be primarily explained by attained abdominal fatness and biomarkers of metabolic dysfunction.

Original language	English
Journal	American Journal of Epidemiology
Volume	185
Issue number	9
Pages (from-to)	751-764
Number of pages	14
ISSN	0002-9262
DOIs	https://doi.org/10.1093/aje/kww194
Publication status	Published - 2017
Externally published	Yes

Keywords

Adiposity
Adult weight gain
Colorectal cancer
Metabolic mediators

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/aje/kww194

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Aleksandrova, K., Schlesinger, S., Fedirko, V., Jenab, M., Bueno-De-Mesquita, B., Freisling, H., Romieu, I., Pischon, T., Kaaks, R., Gunter, M. J., Dahm, C. C., Overvad, K., Rostgaard-Hansen, A. L., Tjønneland, A., Trichopoulou, A., Bamia, C., Lagiou, P., Agnoli, C., Mattiello, A., ... Boeing, H. (2017). Metabolic mediators of the association between adult weight gain and colorectal cancer: Data from the european prospective investigation into cancer and nutrition (EPIC) cohort. American Journal of Epidemiology, 185(9), 751-764. https://doi.org/10.1093/aje/kww194

Metabolic mediators of the association between adult weight gain and colorectal cancer : Data from the european prospective investigation into cancer and nutrition (EPIC) cohort. / Aleksandrova, Krasimira; Schlesinger, Sabrina; Fedirko, Veronika et al.

In: American Journal of Epidemiology, Vol. 185, No. 9, 2017, p. 751-764.

Research output: Contribution to journal › Journal article › Research › peer-review

Aleksandrova, K, Schlesinger, S, Fedirko, V, Jenab, M, Bueno-De-Mesquita, B, Freisling, H, Romieu, I, Pischon, T, Kaaks, R, Gunter, MJ, Dahm, CC, Overvad, K, Rostgaard-Hansen, AL , Tjønneland, A, Trichopoulou, A, Bamia, C, Lagiou, P, Agnoli, C, Mattiello, A, Bradbury, K, Khaw, KT, Riboli, E & Boeing, H 2017, 'Metabolic mediators of the association between adult weight gain and colorectal cancer: Data from the european prospective investigation into cancer and nutrition (EPIC) cohort', American Journal of Epidemiology, vol. 185, no. 9, pp. 751-764. https://doi.org/10.1093/aje/kww194

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title = "Metabolic mediators of the association between adult weight gain and colorectal cancer: Data from the european prospective investigation into cancer and nutrition (EPIC) cohort",

abstract = "Evidence indicates that gaining weight in adult life is associated with an elevated risk of colorectal cancer; however, biological mechanisms that may explain this association remain unclear. We evaluated the mediation effect of 20 different biomarkers on the relationship between adult weight gain and colorectal cancer, using data from a prospective nested case-control study of 452 incident cases diagnosed between 1992 and 2003 and matched within risk sets to 452 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The proportions of mediated effects (%) were estimated on the basis of differences in percent effect changes in conditional logistic regression models with and without additional adjustment for individual biomarkers. Greater adult weight gain (≥300 g/year vs. <300 g/year) was associated with a higher risk of colon cancer (multivariableadjusted relative risk = 1.54, 95% confidence interval: 1.07, 2.24) but not rectal cancer (relative risk = 1.07, 95% confidence interval: 0.68, 1.66). This association was accounted for mostly by attained waist circumference (reduction of 61%) and by the biomarkers soluble leptin receptor (reduction of 43%) and glycated hemoglobin (reduction of 28%). These novel data suggest that the observed association between adult weight gain and colon cancer could be primarily explained by attained abdominal fatness and biomarkers of metabolic dysfunction.",

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author = "Krasimira Aleksandrova and Sabrina Schlesinger and Veronika Fedirko and Mazda Jenab and Bas Bueno-De-Mesquita and Heinz Freisling and Isabelle Romieu and Tobias Pischon and Rudolf Kaaks and Gunter, {Marc J.} and Dahm, {Christina C.} and Kim Overvad and Rostgaard-Hansen, {Agnetha Linn} and Anne Tj{\o}nneland and Antonia Trichopoulou and Christina Bamia and Pagona Lagiou and Claudia Agnoli and Amalia Mattiello and Kathryn Bradbury and Khaw, {Kay Tee} and Elio Riboli and Heiner Boeing",

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T2 - Data from the european prospective investigation into cancer and nutrition (EPIC) cohort

AU - Aleksandrova, Krasimira

AU - Schlesinger, Sabrina

AU - Fedirko, Veronika

AU - Jenab, Mazda

AU - Bueno-De-Mesquita, Bas

AU - Freisling, Heinz

AU - Romieu, Isabelle

AU - Pischon, Tobias

AU - Kaaks, Rudolf

AU - Gunter, Marc J.

AU - Dahm, Christina C.

AU - Overvad, Kim

AU - Rostgaard-Hansen, Agnetha Linn

AU - Tjønneland, Anne

AU - Trichopoulou, Antonia

AU - Bamia, Christina

AU - Lagiou, Pagona

AU - Agnoli, Claudia

AU - Mattiello, Amalia

AU - Bradbury, Kathryn

AU - Khaw, Kay Tee

AU - Riboli, Elio

AU - Boeing, Heiner

PY - 2017

Y1 - 2017

N2 - Evidence indicates that gaining weight in adult life is associated with an elevated risk of colorectal cancer; however, biological mechanisms that may explain this association remain unclear. We evaluated the mediation effect of 20 different biomarkers on the relationship between adult weight gain and colorectal cancer, using data from a prospective nested case-control study of 452 incident cases diagnosed between 1992 and 2003 and matched within risk sets to 452 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The proportions of mediated effects (%) were estimated on the basis of differences in percent effect changes in conditional logistic regression models with and without additional adjustment for individual biomarkers. Greater adult weight gain (≥300 g/year vs. <300 g/year) was associated with a higher risk of colon cancer (multivariableadjusted relative risk = 1.54, 95% confidence interval: 1.07, 2.24) but not rectal cancer (relative risk = 1.07, 95% confidence interval: 0.68, 1.66). This association was accounted for mostly by attained waist circumference (reduction of 61%) and by the biomarkers soluble leptin receptor (reduction of 43%) and glycated hemoglobin (reduction of 28%). These novel data suggest that the observed association between adult weight gain and colon cancer could be primarily explained by attained abdominal fatness and biomarkers of metabolic dysfunction.

AB - Evidence indicates that gaining weight in adult life is associated with an elevated risk of colorectal cancer; however, biological mechanisms that may explain this association remain unclear. We evaluated the mediation effect of 20 different biomarkers on the relationship between adult weight gain and colorectal cancer, using data from a prospective nested case-control study of 452 incident cases diagnosed between 1992 and 2003 and matched within risk sets to 452 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The proportions of mediated effects (%) were estimated on the basis of differences in percent effect changes in conditional logistic regression models with and without additional adjustment for individual biomarkers. Greater adult weight gain (≥300 g/year vs. <300 g/year) was associated with a higher risk of colon cancer (multivariableadjusted relative risk = 1.54, 95% confidence interval: 1.07, 2.24) but not rectal cancer (relative risk = 1.07, 95% confidence interval: 0.68, 1.66). This association was accounted for mostly by attained waist circumference (reduction of 61%) and by the biomarkers soluble leptin receptor (reduction of 43%) and glycated hemoglobin (reduction of 28%). These novel data suggest that the observed association between adult weight gain and colon cancer could be primarily explained by attained abdominal fatness and biomarkers of metabolic dysfunction.

KW - Adiposity

KW - Adult weight gain

KW - Colorectal cancer

KW - Metabolic mediators

U2 - 10.1093/aje/kww194

DO - 10.1093/aje/kww194

M3 - Journal article

C2 - 28387787

AN - SCOPUS:85020180717

SN - 0002-9262

VL - 185

SP - 751

EP - 764

JO - American Journal of Epidemiology

JF - American Journal of Epidemiology

IS - 9

ER -

Metabolic mediators of the association between adult weight gain and colorectal cancer: Data from the european prospective investigation into cancer and nutrition (EPIC) cohort

Abstract

Keywords

UN SDGs

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