Scientists unlock further prostate cancer secrets

Cancer Research UK

Cancer Research UK-funded scientists have taken a further step to identifying men at a greater risk of prostate cancer with the discovery of seven new variants in the human genome that increase the chances of developing the disease. The research is published today (Sunday) in Nature Genetics1.

The international team2 of scientists, led by researchers at The Institute of Cancer Research (ICR) and the University of Cambridge, studied the genes of almost 60,000 men and found seven new regions across the genome that increase the risk. They were on chromosomes 2, 3, 5, 6, 12 and X.

Lead author Professor Ros Eeles from the ICR and the Royal Marsden Hospital said: “We have now found more than 40 of these regions that cumulatively increase a man’s risk of prostate cancer. Together they account for around 25 per cent of the inherited risk. This means that the one per cent of men who carry most of these 40 variants are about four times more likely than an average person to have prostate cancer, giving them a nearly one in two chance of developing the disease.

“We do not yet know whether this is a type of prostate cancer that needs earlier treatment and we are doing further work to determine this. These results bring nearer the day when we can use genetics to tailor our screening and treatment of men at risk of this disease.’’

To identify these regions, the researchers studied 1,536 SNPs - pieces of DNA that vary between individuals - that previous studies had suggested may increase the risk of prostate cancer.
A number of these SNPs were found in genes that are known to be involved in other cancers and diseases.

The variant on chromosome 3 lies in a gene called ZBTB38, which is involved in controlling cell death. This SNP has also been associated with height and previous studies have linked tallness with an elevated risk of prostate cancer.

One of the regions found in the study, in the TERT gene on chromosome 5, was more strongly linked to prostate cancer than previously thought. This gene has previously been linked with a number of cancers including lung, bladder and testicular cancer. It plays a key role in maintaining the length and ends of chromosomes. A number of studies have linked the shortening of chromosomes to an increased risk of cancer making it a possible candidate for developing new treatments.

However, the variant found in this study is in a different region of the gene to those linked to other cancers, suggesting that this particular variant is unique to prostate cancer. Using data on the health of the men in the study the researchers were also able to link this SNP to an increase in PSA level.

Another new SNP found on chromosome 5 is in a gene called FGF10 that is often switched on in breast cancers and there is some evidence that suggests it plays a role in the growth of normal prostate cells.

One of the SNPs found in this study, on chromosome six in the gene CCHCR1, has also been linked to the inflammatory condition psoriasis and this gene is also switched on in skin cancer.
Prostate cancer is the most common cancer in men in the UK. A quarter of all new cases of cancer diagnosed in men are prostate cancers. In 2008, around 37,000 men in the UK were diagnosed with the disease. Each year around 10,000 men in the UK die from prostate cancer.

Dr Julie Sharp, senior science information manager at Cancer Research UK, said: “This type of research is vital to understanding more about prostate cancer and will help researchers to find new ways to prevent the disease and develop more targeted treatments.

“Genome wide association studies are a powerful tool to find common factors that increase the risk of developing cancer and this is an area that Cancer Research UK has been committed to for a number of years. This work has been made possible thanks to the generosity of the public. We are now entering an exciting period when this research will begin to have a real benefit for cancer patients.”

ENDS

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References

1. Kote-Jarai, Z et al, Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study Nature Genetics (2011)

Notes to Editor

2. The international team of researchers were based at: The Institute of Cancer Research; University of Cambridge; The Cancer Council Victoria, Australia; University of Melbourne, Australia; Tampere University Hospital, Finland; Herlev University Hospital, Denmark; German Cancer Research Centre, Germany; Imperial College London; University of Oxford; Karolinska Institute, Sweden; Harvard School of Public Health, USA; American Cancer Society, USA; University of Southern California Keck School of Medicine, USA; National Institutes of Health, USA; Cancer Research UK Cambridge Research Institute; University of Bristol; University of Southern California, USA; Fred Hutchinson Cancer Research Centre, USA; University of Washington, USA; Aarhus University Hospital, Denmark; Hanover Medical School, Germany; University of Tasmania, Australia; Pomeranian Medical University, Poland; Queensland Institute of Medical Research, Australia; Queensland University of Technology, Australia; Griffith University, Australia; Viertel Centre for Research in Cancer Control, Australia; University of Queensland, Australia; Mayo Clinic, USA; Cancer Prevention Institute of California, USA; Stanford University, USA; University Hospital Ulm, Germany; University of Michigan Medical School, USA; H. Le Moffit Cancer Centre, USA; University of Utah School of Medicine, USA; George E. Wahlen Department of Veterans Medical Center, USA; Akita University Graduate School of Medicine, USA.