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Int J Mol Epidemiol Genet 2010;1(4):248-272.
Review Article
Metabolic imbalance and prostate cancer progression
Anya J. Burton, Kate M. Tilling, Jeff M. Holly, Freddie C. Hamdy, Mari-Anne E. Rowlands, Jenny L. Donovan, Richard M. Martin
Department of Social Medicine, University of Bristol, Bristol, UK; MRC Centre for Causal Analysis in Translational
Epidemiology, University of Bristol, Bristol, UK; Clinical Sciences North Bristol, University of Bristol, Bristol, UK; Nuffield
Department of Surgery, University of Oxford, UK.
Received June 25, 2010; accepted July 20, 2010; available online July 25, 2010
Abstract: There is substantial evidence implicating environmental factors in the progression of prostate cancer. The
metabolic consequences of a western lifestyle, such as obesity, insulin resistance and abnormal hormone production
have been linked to prostate carcinogenesis through multiple overlapping pathways. Insulin resistance results in
raised levels of the mitogens insulin and insulin-like growth factor-1, both of which may affect prostate cancer directly,
or through their effect on other metabolic regulators. Obesity is associated with abnormal levels of adipocytederived
peptides (adipokines), sex hormones and inflammatory cytokines. Adipokines have been shown to influence
prostate cancer in both cell culture studies and observational, population level studies. Testosterone appears to have
a complex relationship with prostate carcinogenesis, and it has been suggested that the lower levels associated with
obesity may select for more aggressive androgen independent prostate cancer cells. Prostatic inflammation, caused
by infection, urinary reflux or dietary toxins, frequently occurs prior to cancer development and may influence progression
to advanced disease. High levels of ω-6 fatty acids in the diet may lead to the production of further inflammatory
molecules that may influence prostate cancer. Increased fatty acid metabolism occurs within tumour cells,
providing a potential target for prostate cancer therapies. Aberrations in amino acid metabolism have also been identified
in prostate cancer tissue, particularly in metastatic cancer. This evidence indicates lifestyle interventions may
be effective in reducing the incidence of clinical disease. However, much more research is needed before recommendations
are made. (IJMEG1006005).
Key words: Prostate cancer, obesity, adipokines, insulin-like growth factors, diabetes, inflammation, metabolism
Full Text PDF
Address all correspondence to:
Anya Burton, BSc
Department of Social Medicine
University of Bristol
Canynge Hall, 39 Whatley Road
Bristol, BS8 2PS, UK.
Tel: +44 (0)1173 313932, Fax +44 (0)117928 7325
E-mail: Anya.Burton@bristol.ac.uk
Review Article
Metabolic imbalance and prostate cancer progression
Anya J. Burton, Kate M. Tilling, Jeff M. Holly, Freddie C. Hamdy, Mari-Anne E. Rowlands, Jenny L. Donovan, Richard M. Martin
Department of Social Medicine, University of Bristol, Bristol, UK; MRC Centre for Causal Analysis in Translational
Epidemiology, University of Bristol, Bristol, UK; Clinical Sciences North Bristol, University of Bristol, Bristol, UK; Nuffield
Department of Surgery, University of Oxford, UK.
Received June 25, 2010; accepted July 20, 2010; available online July 25, 2010
Abstract: There is substantial evidence implicating environmental factors in the progression of prostate cancer. The
metabolic consequences of a western lifestyle, such as obesity, insulin resistance and abnormal hormone production
have been linked to prostate carcinogenesis through multiple overlapping pathways. Insulin resistance results in
raised levels of the mitogens insulin and insulin-like growth factor-1, both of which may affect prostate cancer directly,
or through their effect on other metabolic regulators. Obesity is associated with abnormal levels of adipocytederived
peptides (adipokines), sex hormones and inflammatory cytokines. Adipokines have been shown to influence
prostate cancer in both cell culture studies and observational, population level studies. Testosterone appears to have
a complex relationship with prostate carcinogenesis, and it has been suggested that the lower levels associated with
obesity may select for more aggressive androgen independent prostate cancer cells. Prostatic inflammation, caused
by infection, urinary reflux or dietary toxins, frequently occurs prior to cancer development and may influence progression
to advanced disease. High levels of ω-6 fatty acids in the diet may lead to the production of further inflammatory
molecules that may influence prostate cancer. Increased fatty acid metabolism occurs within tumour cells,
providing a potential target for prostate cancer therapies. Aberrations in amino acid metabolism have also been identified
in prostate cancer tissue, particularly in metastatic cancer. This evidence indicates lifestyle interventions may
be effective in reducing the incidence of clinical disease. However, much more research is needed before recommendations
are made. (IJMEG1006005).
Key words: Prostate cancer, obesity, adipokines, insulin-like growth factors, diabetes, inflammation, metabolism
Full Text PDF
Address all correspondence to:
Anya Burton, BSc
Department of Social Medicine
University of Bristol
Canynge Hall, 39 Whatley Road
Bristol, BS8 2PS, UK.
Tel: +44 (0)1173 313932, Fax +44 (0)117928 7325
E-mail: Anya.Burton@bristol.ac.uk
