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US researchers identify possible 'high risk' prostate cancer gene
Wednesday 11 January 2012
Researchers in the US have found that faults in a gene called HOXB13 seem to be more common in men with an inherited form of prostate cancer, and among those who develop the disease at a younger age.
According to the study, published in the New England Journal of Medicine, men who carry this mutation - which is rare in the general population - have a 10 to 20 times higher risk of developing prostate cancer.
Although the results need to be fully confirmed in larger studies, it opens up new avenues of research, and scientists believe that understanding how the gene is involved in prostate cancer may lead to better ways to diagnose and manage the disease.
The team, based at the Johns Hopkins University School of Medicine and the University of Michigan examined DNA samples from young prostate cancer patients from 94 different families.
The men all had multiple cases of the disease among their immediate relatives.
The team used 'next generation' DNA sequencing to analyse more than 200 different genes near a part of the human genome - chromosome 17q - that had previously been linked to inherited or early-onset prostate cancer.
This revealed that that 18 of the men, from four different families, all had the same fault in one these genes - HOXB13.
HOX13B has an important role in the development of the prostate in babies in the womb, and in thought to be involved in regulating its function in later life.
Most interestingly, HOXB13 is known to interact with a protein called the androgen receptor - a key player in prostate cancer growth.
To further investigate their findings, the researchers then studied samples from 5,100 prostate cancer patients treated at either Johns Hopkins or University of Michigan.
They found that the HOXB13 mutation was present in 1.4 per cent of these patients, and that these men were much more likely to have at least one first-degree relative - a father or brother - who had also been diagnosed.
By contrast, they only found HOX13B faults in 0.1 per cent of healthy men.
Senior author Dr Kathleen A Cooney said: "This is the first major genetic variant associated with inherited prostate cancer."
Another author on the study, Dr William B Isaacs, added: "It's what we've been looking for over the past 20 years. It's long been clear that prostate cancer can run in families, but pinpointing the underlying genetic basis has been challenging."
Professor Ros Eeles, a Cancer Research UK-funded cancer geneticist from The Institute of Cancer Research and The Royal Marsden Hospital, said it fitted in with the picture of prostate cancer genetics that had been building up over several decades.
"We think that prostate cancer genetics is a mixture of 'lower risk' gene variants that are common in the population, and rarer 'higher risk' variants," she said.
Forty-six low-risk variants have been identified to date, many by researchers funded by Cancer Research UK, including Professor Eeles's group and that of Professor Doug Easton in Cambridge.
The more of these variants a man carries, the greater his chances of developing prostate cancer.
She added, "This new study is interesting, as it used next-generation sequencing to analyse the genes within a region of the genome (17q) known to be linked to high risk prostate cancer families,"
"But it will be important to validate these findings in larger studies. My team, along with Professor Easton's team, coordinates a large international consortium, PRACTICAL, which has access to over 50,000 samples from prostate cancer cases and controls from 34 groups worldwide, in which such variants can be tested".
Professor Eeles also said she expected that other large international research projects, such as the International Cancer Genome Consortium, is likely to identify more such variants over the coming years.
Copyright Press Association 2012
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“It will be important to validate these findings in larger studies”
Professor Ros Eeles, Cancer Research UK
