Community Research and Development Information Service - CORDIS

ERC

BARCODE Report Summary

Project ID: 339208
Funded under: FP7-IDEAS-ERC
Country: United Kingdom

Periodic Report Summary 2 - BARCODE (The use of genetic profiling to guide prostate cancer targeted screening and cancer care)

The BARCODE project is divided into two studies which are aiming to utilise knowledge of the genetic risk of prostate cancer to target screening to high risk men in the community, and also to offer effective treatment options to men who develop prostate cancer based on inherited (germline) mutations in their genes.
The first study, BARCODE1, has led to the development of a genetic profile which includes 170 common genetic variants (markers) that can be studied in European populations to identify men at increased risk of developing prostate cancer and allow them to undergo screening.
The genetic profile used in this study consists of a SNP (single nucleotide polymorphism) assay incorporating 170 SNPs. These are made up of the previously reported 100 prostate cancer risk SNPs as well as the latest 65 risk SNPs identified by the OncoArray meta-analysis of 142,000 men (presented at American Society of Human Genetics Conference 2016). This assay will be used to genotype 5000 men from the community in this study and a polygenic risk score will be calculated for each individual based on their genotype. Men in the top 10% of the risk profile will be offered prostate cancer screening by MRI (magnetic resonance imaging) and biopsy.
The pilot study is currently recruiting men, aged 55-69 years, from the community via their general practitioners so that they can undergo the genetic test. Once the pilot study has completed recruitment, the main study will commence and aims to recruit a total of 5000 men.
The second study, BARCODE2, has produced a custom designed gene panel which will be used in men who have advanced prostate cancer to test their DNA for germline mutations in DNA repair genes. The custom gene panel is based on target exon capture of 115, mainly DNA repair, genes. These genes were chosen based on recently published data indicating a higher than expected frequency of germline mutations in men with advanced prostate cancer.

Men who are found to have a mutation in the study will be offered treatment with 3 weekly carboplatin chemotherapy for up to 10 cycles of treatment. This is a drug that is not usually received by men with advanced prostate cancer, but research evidence suggests that the majority of men with germline mutations in DNA repair genes will benefit from treatment with this drug. For example, a high response rate has been reported with PARP inhibitor treatment of men with advanced prostate cancer (88% response rate, reported by Mateo et al 2015, New England Journal of Medicine). From the more extensive studies in the ovarian cancer setting, there is a known cross-sensitivity between PARP inhibitors and platinum chemotherapy, especially in women with mutations in DNA repair genes such as BRCA1/2. The BARCODE2 study is the first prospective study to utilise a DNA repair gene panel to target carboplatin chemotherapy to men with metastatic castration resistant prostate cancer and a germline genetic mutation. The study has recently opened and will recruit ~450 men with advanced prostate cancer.

Reported by

INSTITUTE OF CANCER RESEARCH - ROYAL CANCER HOSPITAL
United Kingdom
Follow us on: RSS Facebook Twitter YouTube Managed by the EU Publications Office Top