A clinical trial including 692 men with confirmed diagnosis of metastatic prostate cancer showed that mutations in DNA repair genes are more frequent (11.8%) in people with metastatic prostate cancer than healthy men (2.7%) and men with a localised prostate tumor (4.6%).
Prostate cancer is the most diagnosed cancer among men in Canada. In their lifetime, 1 out of 8 men will receive a diagnostic of this type of cancer, representing 24 thousand new cases in 2015. Hopefully, this cancer can be cured and as only 17% will be expected to die from it. Moreover, progresses in treatments and early diagnosis of the disease have reduced the mortality rate by about 4% every year between 2001 and 2009.
This cancer is known to be familial, meaning that having a parent with a prostate cancer increases your risk of suffering from the same disease. That also means that there are genetic implications and that those mutations can be inherited from the parents. Similar to many of the breast cancer cases, those inherited mutations are likely to be located in genes that produce proteins responsible for DNA reparation, since those proteins are responsible for preventing other mutations from happening. While it is known that the prevalence of DNA-repair gene mutations is normal for men with benign prostate cancer, the frequency of those mutations in men with metastatic prostate cancer is unknown.
Teams of researchers from USA and UK investigated this question in a clinical trial published in the prestigious New England Journal of Medicine. They recruited 692 men with confirmed diagnosis of metastatic prostate cancer and performed multiplex sequencing assays to identify mutations in 20 DNA-repair genes with a known association with cancer. Patients were not selected based on family history of cancer.
Their results showed that mutations in DNA repair genes are more frequent in people with metastatic prostate cancer than healthy men and men with localised prostate tumor. In 11.8% of the participants, mutations in DNA-repair genes were identified. Those mutations were located in 16 different proteins with the highest frequency found in BRCA2, ATM, CHEK2, BRCA1, RAD51 and PALB2. The normal prevalence of mutations in DNA-repair genes in the population is 2.7% and 4.6% in the population with localized prostate cancer.
This study will certainly result in a better diagnostic, classification and treatment of this deadly cancer.
Written By: Jean-Michel Bourget, PhD