Genetic Susceptibility

Author
Dr Ros Eeles ros@icr.ac.uk
Institute of Cancer Research

Investigation is taking place into the genetic predisposition to prostate cancer. The research includes the identification of high and low penetrance genes and the role of gene-environment interactions. The biggest, and oldest study began in 1992 and involves a nationwide programme to identify families with a familial susceptibility to prostate cancer, especially those under 60 years of age at diagnosis and/or families with three or more prostate cancer cases.

The aim is to recruit 6000 patients with prostate cancer before 2010. To date there have been 4000 patients identified in the UK that are eligible for the study, with 2600 patients fully consented and participating already. Currently, there are 220 collaborators including urologists, oncologists, geneticists, and research nurses across the UK who refer patients into the study to help achieve the project targets.

The research team also collaborates with a number of other centres around the UK. Links have been established with Nottingham University, to conduct a gene-environment interaction study, coordinated by Dr Ken Muir and Dr Tim Key. This project is funded by the Prostate Cancer Charitable Trust. Another study, situated at the Royal Marsden Hospital & the Institute of Cancer Research and funded by the Prostate Research Charity UK, is looking at the effects of irradiation in men with a genetic predisposition to prostate cancer. In addition, the research team is studying the effects of the genetic make-up of the immune system with Dr Martin Howell at Southampton, funded by the Wessex Cancer Charity.

Future plans for the team are likely to include the use of the human genome sequence to identify prostate cancer genes, as well as identification of more patients via the NCRN network.

A breakdown of the 2600 patients that have consented to the study, June 2002:
PRM - 1862 Royal Marsden prostate cancer patients identified. This represents the systematic series of the study (target 4000).
PRS - 276 patients identified with a family history of prostate cancer e.g. siblings, fathers, grandfathers and uncles etc. (target 1000).
PRT - 46 patients identified from the Thames Cancer Registry.
PRY - 416 patients identified that are all <60yrs at diagnosis i.e. young patients (target 1000).

Explanation of the graphs.

Graph 1 - RMH (PRM) Patients Consented by Year of Consent.

The top graph demonstrates a graphical representation of the average number of RMH patients that are consenting and entering the familial prostate cancer study every week (~9). The lower graph shows the average number of RMH patients that have entered the study each year since the study begun, with a target of 445 for 2002.

Graph 2 - RMH (PRM) Patients Consented Each Week, since 2001, on a Cumulative Basis.

This graph demonstrates the number of patients that have consented each week, over the last 18 months, comparing figures week-by-week for 2001 and 2002.

Recent Publications.
1) Kote-Jarai Z, Easton D, Edwards SM, Jefferies S, Jackson RA, Ardern-Jones A, Murkin A, Durocher F, Dearnaley DP, Singh R, Shearer R, Kirby R, The CRC/BPG UK Familial Prostate Cancer Study Collaborators, Houlston R, Eeles RA. (2001). Relationship between Glutathione S-Transferase M1, P1 and T1 polymorphisms and early onset prostate cancer. Pharmacogenetics 11: 325-330.

2) Sarah L. McCarron, Stephen Edwards, Philip R. Evans, Roz Gibbs, David P. Dearnaley, Anna Dowe, Christine Southgate, The Cancer Research Campaign/British Prostate Group United Kingdom Familial Prostate Cancer Study Collaborators, Douglas F. Easton, Rosalind A. Eeles and W. Martin Howell. Influence of Cytokine Gene Polymorphisms on the Development of Prostate Cancer. Cancer Res. 2002 62: 3369-3372.

3) Z Kote-Jarai, F Durocher, S M Edwards, R Hamoudi, R A Jackson, A Ardern-Jones, A Murkin, D P Dearnaley, R Kirby, R Houlston, D F Easton, R Eeles and the CRC?BPG UK Familial Prostate Cancer Collaborators. Association between the GCG polymorphism of the selenium dependent GPX1 gene and the risk of young onset prostate cancer. Prostate Cancer and Prostatic Diseases (2002) 5, No 3, 189-192.

4) J C Meitz, S M Edwards, D F Easton, A Murkin, A Ardern-Jones, R A Jackson, S Williams, D P Dearnaley, M R Stratton, R S Houlston. The Cancer Research UK/BPG UK Familial Prostate Cancer Study Collaborators and R A Eeles. HPC2/ELAC2 polymorphisms and prostate cancer risk: analysis by age of onset of disease. British Journal of Cancer 2002 87, No. 8, 905 - 908.