Advanced prostate cancer accounts for up to 15% of all prostate cancer diagnoses.
In a long-term study, scientists from the Institute of Cancer Research (ICR) have identified new inherited gene mutations associated with aggressive prostate cancer.
Published in European Society of Genitourinary OncologyFindings from the UK Hereditary Prostate Cancer Study (UKGPCS) could help clinicians to identify certain prostate cancer men who are at high risk of rapidly progressing disease.
Prostate cancer is currently the most common cancer in UK men, causing around 55,100 new cases each year.
Advanced prostate cancer accounts for up to 15% of all prostate cancer diagnoses.
The researchers used data from the ongoing UKGPCS and six substudies that sequenced the same 10 candidates in participant samples, and conducted an analysis that included 6,805 prostate cancer cases, of which 3,548 were advanced.
The team looked for germline mutations that occur in patients’ eggs or sperm and affect every cell in an individual’s body.
The researchers focused on genetic changes called putative loss-of-function mutations, which prevent the production or activation of proteins encoded by the affected genes, and looked for associations with malignant diseases such as prostate cancer that have metastasized, reached a certain stage or grade, or become fatal.
The researchers found suspected loss-of-function mutations in four genes associated with aggressive prostate cancer — ATM, MLH1, MSH2, and NBN — and also confirmed a previously identified association between BRCA2 mutations and prostate cancer aggressiveness.
Ross Eales, Professor of Tumor Genetics at the ICR, who leads the UKGPCS, said: “Our study confirms that people who inherit loss-of-function mutations in ATM, BRCA2, MLH1, MSH2 and NBN are at highest risk of aggressive prostate cancer.
“Now we need to find ways to determine which patients need urgent care and which are candidates for active surveillance.”
