Final Report Summary - BARCODE (The use of genetic profiling to guide prostate cancer targeted screening and cancer care)
The BARCODE project is divided into two studies (BARCODE 1 and BARCODE 2) which aim 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, BARCODE 1, has led to the development of a genetic profile which includes 130 common genetic variants (markers) that can be analysed in DNA from a saliva sample. This genetic profile can be studied in men of European ancestry to identify those who are at increased risk of developing prostate cancer and enable them to undergo screening. The genetic profile used in this study consists of a 130 SNP assay, which is the most optimal applicable to men of European origin. This assay is being used in this study to genotype 5000 men from the community and a polygenic risk score is calculated for each individual based on their genotype. Men in the top 10% of the risk profile are offered prostate cancer screening using MRI (Magnetic Resonance Imaging) and biopsy. The BARCODE 1 pilot study completed recruitment of healthy men aged 55-69 years of European ancestry via GPs in England and all men underwent genetic testing and prostate screening. Following the pilot study, the full study was launched and has recruited over 5000 men, who are now undergoing 5 years of follow-up so that cancer incidence can be determined. To date 157 men in the top 10% of the risk profile have undergone MRI and 24 have had cancer diagnosed at biopsy.
The second study, BARCODE 2 produced a custom-designed gene panel for sequencing which is used in men who have advanced prostate cancer to test their DNA for germline mutations in DNA repair genes. These genes were chosen based on data published, by our group and others, 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 undergo 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. New England Journal of Medicine, 2015). 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 and BRCA2. The BARCODE 2 trial 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 trial is successfully recruiting, with 176 men enrolled to date, with 18% having a germline DNA repair gene mutation making them eligible for treatment.
The results of this grant award and our outputs to date have enabled further funding to be leveraged from Cancer Research UK to support the additional follow-up of the BARCODE1 participants for a further 5 years to look at cancer incidence within this population. Further funding has also been awarded from the TANDEM programme grant from the Novo Nordisk Foundation to expand and complete the BARCODE2 study.
The first study, BARCODE 1, has led to the development of a genetic profile which includes 130 common genetic variants (markers) that can be analysed in DNA from a saliva sample. This genetic profile can be studied in men of European ancestry to identify those who are at increased risk of developing prostate cancer and enable them to undergo screening. The genetic profile used in this study consists of a 130 SNP assay, which is the most optimal applicable to men of European origin. This assay is being used in this study to genotype 5000 men from the community and a polygenic risk score is calculated for each individual based on their genotype. Men in the top 10% of the risk profile are offered prostate cancer screening using MRI (Magnetic Resonance Imaging) and biopsy. The BARCODE 1 pilot study completed recruitment of healthy men aged 55-69 years of European ancestry via GPs in England and all men underwent genetic testing and prostate screening. Following the pilot study, the full study was launched and has recruited over 5000 men, who are now undergoing 5 years of follow-up so that cancer incidence can be determined. To date 157 men in the top 10% of the risk profile have undergone MRI and 24 have had cancer diagnosed at biopsy.
The second study, BARCODE 2 produced a custom-designed gene panel for sequencing which is used in men who have advanced prostate cancer to test their DNA for germline mutations in DNA repair genes. These genes were chosen based on data published, by our group and others, 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 undergo 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. New England Journal of Medicine, 2015). 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 and BRCA2. The BARCODE 2 trial 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 trial is successfully recruiting, with 176 men enrolled to date, with 18% having a germline DNA repair gene mutation making them eligible for treatment.
The results of this grant award and our outputs to date have enabled further funding to be leveraged from Cancer Research UK to support the additional follow-up of the BARCODE1 participants for a further 5 years to look at cancer incidence within this population. Further funding has also been awarded from the TANDEM programme grant from the Novo Nordisk Foundation to expand and complete the BARCODE2 study.