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Volume 10
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Article

A Metabolomics Analysis of Adiposity and Advanced Prostate Cancer Risk in the Health Professionals Follow-Up Study

by
Barbra A. Dickerman
1,*,
Ericka M. Ebot
1,
Brian C. Healy
2,3,4,
Kathryn M. Wilson
1,5,
A. Heather Eliassen
1,5,
Alberto Ascherio
1,5,6,
Claire H. Pernar
1,
Oana A. Zeleznik
5,
Matthew G. Vander Heiden
7,8,
Clary B. Clish
9,
Edward Giovannucci
1,5,6 and
Lorelei A. Mucci
1,5
1
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
2
Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
3
Partners Multiple Sclerosis Center, Brigham and Women’s Hospital, Boston, MA 02115, USA
4
Biostatistics Center, Massachusetts General Hospital, Boston, MA 02114, USA
5
Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
6
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
7
Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
8
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
9
Broad Institute of Massachusetts, Institute of Technology and Harvard, Boston, MA 02142, USA
*
Author to whom correspondence should be addressed.
Metabolites 2020, 10(3), 99; https://doi.org/10.3390/metabo10030099
Submission received: 10 January 2020 / Revised: 28 February 2020 / Accepted: 7 March 2020 / Published: 10 March 2020
(This article belongs to the Special Issue Integrative-Metabolomics in Epidemiological Studies)
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Abstract

Obesity is associated with a higher risk of advanced prostate cancer, but men with the same body mass index (BMI) may differ in their underlying metabolic health. Using metabolomics data from nested case-control studies in the Health Professionals Follow-Up Study, we calculated Pearson correlations between 165 circulating metabolites and three adiposity measures (BMI, waist circumference, and derived fat mass from a validated prediction equation) to identify adiposity-associated metabolites. We used Lasso to further select metabolites for prediction models of adiposity measures, which we used to calculate metabolic scores representing metabolic obesity. In an independent set of 212 advanced prostate cancer cases (T3b/T4/N1/M1 or lethal during follow-up) and 212 controls, we used logistic regression to evaluate the associations between adiposity measures and metabolic scores with risk of advanced disease. All adiposity measures were associated with higher blood levels of carnitines (Pearson r range, 0.16 to 0.18) and lower levels of glutamine (r = −0.19) and glycine (r, −0.29 to −0.20), in addition to alterations in various lipids. No adiposity measure or metabolic score was associated with risk of advanced prostate cancer (e.g., odds ratio for a 5 kg/m2 increase in BMI 0.96 (95% CI: 0.73, 1.27) and BMI metabolic score 1.18 (95% CI: 0.57, 2.48)). BMI, waist circumference, and derived fat mass were associated with a broad range of metabolic alterations. Neither adiposity nor metabolic scores were associated with risk of advanced prostate cancer.
Keywords: adiposity; epidemiology; fat mass; metabolomics; obesity; advanced prostate cancer; waist circumference adiposity; epidemiology; fat mass; metabolomics; obesity; advanced prostate cancer; waist circumference

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MDPI and ACS Style

Dickerman, B.A.; Ebot, E.M.; Healy, B.C.; Wilson, K.M.; Eliassen, A.H.; Ascherio, A.; Pernar, C.H.; Zeleznik, O.A.; Vander Heiden, M.G.; Clish, C.B.; et al. A Metabolomics Analysis of Adiposity and Advanced Prostate Cancer Risk in the Health Professionals Follow-Up Study. Metabolites 2020, 10, 99. https://doi.org/10.3390/metabo10030099

AMA Style

Dickerman BA, Ebot EM, Healy BC, Wilson KM, Eliassen AH, Ascherio A, Pernar CH, Zeleznik OA, Vander Heiden MG, Clish CB, et al. A Metabolomics Analysis of Adiposity and Advanced Prostate Cancer Risk in the Health Professionals Follow-Up Study. Metabolites. 2020; 10(3):99. https://doi.org/10.3390/metabo10030099

Chicago/Turabian Style

Dickerman, Barbra A., Ericka M. Ebot, Brian C. Healy, Kathryn M. Wilson, A. Heather Eliassen, Alberto Ascherio, Claire H. Pernar, Oana A. Zeleznik, Matthew G. Vander Heiden, Clary B. Clish, and et al. 2020. "A Metabolomics Analysis of Adiposity and Advanced Prostate Cancer Risk in the Health Professionals Follow-Up Study" Metabolites 10, no. 3: 99. https://doi.org/10.3390/metabo10030099

APA Style

Dickerman, B. A., Ebot, E. M., Healy, B. C., Wilson, K. M., Eliassen, A. H., Ascherio, A., Pernar, C. H., Zeleznik, O. A., Vander Heiden, M. G., Clish, C. B., Giovannucci, E., & Mucci, L. A. (2020). A Metabolomics Analysis of Adiposity and Advanced Prostate Cancer Risk in the Health Professionals Follow-Up Study. Metabolites, 10(3), 99. https://doi.org/10.3390/metabo10030099

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