Early detection of prostate cancer in the general practice setting: The BARCODE1 Study

Background The discovery of the code of the human genome has led to the anticipation that this will be able to transform healthcare.

It is hoped that this will enable identification of individuals who have a higher risk of certain diseases which opens up the possibility of risk stratification for early detection.

We therefore expect that early detection of cancer can be targeted to such higher risk groups who would have (i) a higher proportion of cancer; (ii) a higher proportion of cancer which needs radical treatment and if detected earlier would be more likely to be cured and (iii) an acceptability of undergoing more intensive screening techniques as such groups have more to gain from targeted more intensive screening methods as their risk of over-diagnosis is lower.

Furthermore, such populations in a higher risk stratum provide greater power for the assessment of new early detection strategies as a smaller sample size is needed to identify statistically significant results using new biomarker methodology.

These three paradigms are embedded in this proposal which aims to capitalise on our previous success in finding genetic risk profiles which predispose to prostate cancer.

Aims -To analyse a 130 SNP polygenic risk score (PRS) in saliva samples from 5000 men aged 55-69-years in General Practice to identify men in the top 10% of the risk distribution to offer earlier prostate cancer detection -To assess the uptake of prostate MP-MRI screening in men in the top 10% of the PRS -To assess the proportion of clinically significant prostate cancer in these men and follow them up to assess outcomes -To assess metabolomic profiling to identify better markers for early detection in prostate cancer in higher risk men.

Methods A saliva test will have genotyping for a 130 SNP profile and men at higher risk from this genetic profiling will be offered MRI of the prostate and biopsy.

This will be correlated with metabolomic measurements of biological fluids to determine a prostate cancer screening algorithm that targets screening to those at higher risk. How the results of this research will be used.

This project will assess if the new genetics can be used to target more intensive prostate analyses (MRI and Biopsy) to find aggressive disease earlier. It will also look for new markers using metabolomics on urine and blood samples. This would alter screening policy in the UK.