Germline Genetic Profiling in Prostate Cancer: Latest Developments and Potential Clinical Applications

Abstract

Familial and twin studies have demonstrated a significant inherited component to prostate cancer predisposition. Genome wide association studies have shown that there are 100 single nucleotide polymorphisms which have been associated with the development of prostate cancer. This review aims to discuss the scientific methods used to identify these susceptibility loci. It will also examine the current clinical utility of these loci, which include the development of risk models as well as predicting treatment efficacy and toxicity. In order to refine the clinical utility of the susceptibility loci, international consortia have been developed to combine statistical power as well as skills and knowledge to further develop models that could be used to predict risk and treatment outcomes.

Prostate cancer is one of the most common cancers to occur in men in the western world. The incidence of prostate cancer is however lower in Asian countries. There are some families who have many male members affected with prostate cancer. The incidence of prostate cancer is also increased in men of Afro-Caribbean ancestry. Studies have shown that there are inherited genetic changes that may be accounting for these differences, however only one third of these changes have been discovered so far. This review aims to discuss how these genetic changes have been discovered and how they can potentially be used in every day clinical practice.

Keywords::

• clinical application
• genetic variation
• genome-wide association study
• prostate cancer
• risk modeling
• single nucleotide polymorphism

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/full/10.4155/fso.15.87

Acknowledgements

The authors would also like to thank the collaborators in the ELLIPSE, PRACTICAL, IMPACT and COGS consortia. The authors acknowledge support from the National Institute for Health Research to the Biomedical Research Centre at The Institute of Cancer Research and Royal Marsden Foundation NHS Trust.

Financial & competing interests disclosure

The authors are supported by funding from The European Community's Seventh Framework Programme under the grant agreement 223175 (grant number Health F2 2009 223175-COGS), the Genetic Associations and Mechanisms in Oncology (GAME-ON) Initiative (NIH ELLIPSE grant: U19CA148537) and CRUK (Cancer Research United Kingdom) grants C5047/A10692 (PRACTICAL) and C5047/A13232 (IMPACT). The authors are grateful for the support from The Ronald and Rita McAulay Foundation, The Institute of Cancer Research Everyman Campaign and Prostate Cancer UK. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.