Metabolic Profile And Prostate Cancer Risk In EPIC

Julie SCHMIDT, University of Oxford, United Kingdom
FENSOM G. 1 , APPLEBY P. 1 , ACHAINTRE D. 2 , GICQUIAU A. 2 , GUNTER M. 2,3 , FERRARI P. 2 , RINALDI S. 2 , SCALBERT A. 2 , KEY T. 1 , TRAVIS, ON BEHALF OF EPIC R. 1

1 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
2 Nutrition and Metabolism Section, IARC, Lyon, France
3 Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London

Purpose
The aetiology of prostate cancer is largely unknown. Elevated circulating insulin-like growth factor I (IGF-I) remains the only established and potentially modifiable risk factor. Protein intake may be positively associated with risk, and diets high in protein can increase circulating IGF-I. Metabolomics may help to clarify the mechanisms underlying these associations and may identify novel risk factors for prostate cancer. For example, dietary amino acids may affect cancer risk through effects on the synthesis of IGF-I and/or by stimulation of the mTOR pathway, which integrates signals from nutrients and growth factors and is an important mediator of cancer progression. We aimed to prospectively investigate the association between pre-diagnostic metabolic profile in plasma and prostate cancer risk.

Methods
A case-control study has been nested within the EPIC cohort, with 2000 cases of prostate cancer and 2000 matched controls. Concentrations of 145 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose and sphingolipids) are being measured at IARC in prediagnostic plasma samples using the BIOCRATES AbsoluteIDQ p180 Kit, a targeted metabolomic assay. Relative risks for prostate cancer in relation to concentrations of individual metabolites and metabolic profiles will be estimated using conditional logistic regression.

Results
Assays from a total of 1000 case-control pairs will be completed by March and these data will be presented at the meeting.
 
Conclusions
This study will provide prospective data on the relationships between plasma metabolites and prostate cancer risk, and will advance our understanding of the relationships between diet, circulating hormones and risk for the disease, as well as the underlying mechanisms. The identification of potentially modifiable metabolic profiles associated with risk, and of correlated dietary and hormonal factors, may inform the future design of effective public health policies aimed at prostate cancer prevention.

Funding: Cancer Research UK, World Cancer Research Fund