Title: Mapping Genetic Variants to Offer a Targeted Prostate Cancer Screening Study in Southern England
Funder: Prostate Cancer UK

Abstract: AIM The aim of our research is to identify prostate cancer predisposition genetic variants to be able to offer genetic profiling. This will be used to identify men at increased risk of prostate cancer to offer targeted screening. SPECIFIC AIM OF THIS APPLICATION The aim of this application is to identify better genetic variants for use in a study of genetic profiling of men which will be undertaken in Southern England. This will enable us to determine who would benefit from targeted prostate cancer screening by using genetic profiling. WHAT ARE WE APPLYING FOR? We are applying for finance to support a member of staff and laboratory consumables to undertake genetic mapping studies. This builds on our current Prostate Action work and will enable us to take findings into a study of targeted prostate screening which will be undertaken in Southern England. BACKGROUND Prostate cancer is the commonest male cancer in the UK with over 40,000 cases occurring per year. Currently population screening based on an age criterion is not recommended by the Department of Health since although such screening has been shown to reduce mortality in a European study, such a screening programme has a high number of false positives and does not target those who are most likely to benefit. The aim of our work is to use genetic risk to identify men at higher risk of prostate cancer who would be most likely to benefit from a targeted screening approach. We have pilot data in 80 men with a family history of prostate cancer that targeting screening to a higher risk group results in the finding of a higher proportion of prostate cancer, a substantial amount of which needs treatment. However only 9% of men have a family history and the rest of the population would need genetic risk profiling to stratify them further to identify those at higher risk, hence this study. There is evidence that a proportion of cases occurs due to a genetic risk factor (an alteration in the genetic code, the blueprint of life) which predisposes to the development of the disease. Some of these genetic variants can be quite common (some occur in over half of men) and each carries only a slightly increased risk of development of prostate cancer, however, just as when one is dealt a different hand in a pack of cards, a combination of these genetic variants can multiply the risks and result in a spectrum of risks. Some of these combinations can result in quite high risks (a risk of prostate cancer nearly 5 times that of the general population). If these variants can be identified then the combination of variants can be used to genetically profile men to be able to target prostate screening to those in the highest risk groups. Our group has so far identified 50 genetic variants associated with prostate cancer (reviewed in Goh et al., 2012; Eeles et al., submitted to Nature Genetics, 2012) but we have evidence from preliminary data (Kote-Jarai et al., 2011) that these are near variants in the genome which are as yet undiscovered and which are associated with higher risks. These higher risk variants could therefore be used to identify men who could be offered targeted prostate cancer screening based on genetic risk profiling. This is the aim of this application.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS