More progress in understanding prostate cancer genetics

Researchers have found new genetic changes linked with prostate cancer

Understanding the causes of cancer is one of the key aims of organisations like Cancer Research UK. But although we’ve made huge progress in identifying risk factors for cancers such as breast and bowel cancer, for others the underlying causes aren’t as clear cut. Prostate cancer is one of these.

To find out more, scientists around the world are studying the genetic changes that are linked to an increased risk of prostate cancer. And this week in the journal Nature Genetics, several groups, including a team of Cancer Research UK-funded scientists announced the discovery of new genetic variations that are linked to the disease.

Professor Doug Easton and Dr Ros Eeles are leading experts in cancer genetics. Together with collaborators across the world they’ve already identified seven genetic changes that increase prostate cancer risk. And their two new studies describe nine more variations that are linked to the disease.

The new genetic variants are known as SNPs (single nucleotide polymorphisms, or ‘snips’). These one-letter alterations in the genetic code act as markers in our genomes, allowing researchers to track specific genes that they think might be involved in the development of a particular cancer. We’ve posted before about how researchers are using SNPs to track down cancer genes.

Seven new variants

The first of Eeles and Easton’s new studies looked at genetic data from 21 studies worldwide involving over 38,000 men, and divided them into two groups – healthy men, and men with prostate cancer. They then looked at over 43,000 different SNPs and identified seven that were more common amongst men with the disease. These new SNPs are on chromosomes 2, 4, 8, 11 and 22.

The new SNPs were found close to specific genes, meaning these genes are likely to be involved in prostate cancer. And in fact two of them, NKX3.1 and ITGA6, have already been suggested by scientists as targets for new cancer treatments. And excitingly, drugs called HDAC1 inhibitors are currently being tested in clinical trials, and could target cancers caused by faults in NKX3.1. The other gene, ITGA6, also looks promising as a candidate for future drug treatments – it plays an important role in cell movement and so could be involved in cancer spread.

Chromosome 8

Their second study concentrated on chromosome 8, as changes in this region have already been linked to prostate and other cancers. They analysed a specific area of chromosome 8 in the genomes of over 10,000 men, again divided into two groups – 5000 with prostate cancer and 5000 healthy men. This study identified two entirely new SNPs, bringing the total number of SNPs associated with prostate cancer in this region to eight.

Other cancers such as breast, bowel and bladder cancer are also associated with changes in chromosome 8. This means that the new research could have wide-ranging implications – as Ros Eeles said in an interview for our main website, as far as cancer’s concerned, “chromosome 8 is a particularly interesting part of the genome.”

Two other studies

It’s been a good week for prostate cancer genetics. As well as the two Cancer Research UK-funded studies, two other papers on the same topic were published in the same issue of Nature Genetics. One identified yet another new region of the genome linked with the disease, and the other independently found one of the two new SNPs on chromosome 8.

So where is this work going to lead?

The next step for Eeles, Easton and their colleagues is to see how their results can help men at risk of prostate cancer. They’ve estimated that around one in 100 men carry most of the genetic variants that have been identified so far. And because the effects of these SNPs add up, they estimate that these men have a lifetime risk of developing prostate cancer of one in five, compared to the average risk of one in ten.

Importantly, a man carrying these variants isn’t certain to develop prostate cancer. A lifetime risk of one in five means that out of every five men carrying all the higher risk variants, only one will develop prostate cancer.

But it’s still valuable to know who is at higher risk of the disease (as the media have reported this week). In the future it may be possible to identify these men and develop targeted screening for them, for example using the PSA test that can detect prostate cancer (although there are problems with the PSA test that we’ve written about before). The aim would be to detect any cancers at an early stage, when treatment should be more effective.

And this work may not only help to diagnose prostate cancer earlier. It could also lead to new treatments or even ways to prevent the disease. Understanding how faults in particular genes could cause prostate cells to become cancerous will lead scientists down new avenues of research. The more we can find out about the causes of prostate cancer, and who is most at risk, the closer we will be to beating it.

Nell

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