An increasingly detailed picture of prostate cancer genetics

New work reveals further clues about prostate cancer

In 2008, in one of our first articles on this blog, we wrote about research that was “set to kick start prostate cancer research”.

We outlined a ‘gene hunting’ expedition by Cancer Research UK scientists Dr Ros Eeles and Professor Doug Easton, in which they studied the differences in the genetic code of over 10,000 men, and identified seven genetic changes that increase prostate cancer risk.

This was big news. Compared with other cancers such as breast and lung cancer, scientists had known little about how prostate cancer developed until this point. Using a groundbreaking ‘genome wide association study’ approach (more on this later), the researchers had effectively uncovered seven new genetic clues.

So what became of this research? Where did these clues lead?

As we pointed out then, this work marked only the beginning of the story.

Mapping genetic risk

Since this initial publication, the researchers have continued their sleuthing and uncovered yet further detail about the genetics of prostate cancer. In fact, Dr Eeles and Professor Easton have become two of the leading lights in genome-wide association studies for cancer.

In these studies, scientists scan DNA taken from thousands of people to look for common single-letter variations – known as SNPs – associated with cancer (you can read more about SNPs in our ‘behind the headlines’ blog post). Like pins on a map, these SNPs highlight certain locations in the genome, pointing researchers towards nearby genes that might be involved in disease.

In 2009, in further publications, the team tacked pins to a further nine sites of the genetic map. This work took the total known number of genetic regions associated with an increased prostate cancer risk to over 20.

At the time, Professor Easton commented:

“Prostate cancer has the greatest number of independent genes affecting risk of any cancer but we still understand very little about how it develops. This study provides new clues about the processes involved, which could be used to aid the development of new treatments in the future.”

Incremental progress towards improved care

Medical research almost always progresses in this incremental way. Like detectives building a case against a suspect, these clues build up over time to reveal an increasingly detailed understanding.

Alone, the clues may not be enough to ‘crack the case’ and improve prostate cancer care, but combined, and as more clues are discovered, researchers edge closer to finding ways to improve things for patients.

New work uncovers yet further clues

In research published today in the journal Nature Genetics, in a study of almost 60,000 men, the team found seven new regions that increase prostate cancer risk.

This research ups the tally of known genetic risk regions in prostate cancer to 40. On their own, each of these variants has a very small effect – but their effects add up. In fact, the one man in every 100 who carries most of these genetic markers is four times more likely to develop prostate cancer than average. In absolute terms, this means he has a 50/50 chance of developing the disease.

So clearly significant progress has been made since the first discovery in early 2008 – but what does this mean for the man on the street?

At the moment – not a lot. For example, we don’t yet know much about what sort of prostate cancer these men will develop. Do they require earlier treatment, or are they unlikely to progress into full-blown disease?

Time – and further research – will tell. But it is likely that these results will soon help doctors to identify men at high risk of prostate cancer, who might benefit from frequent check-ups or testing.

Clues pointing to suspects

What’s also exciting about this most recent work is that the SNPs discovered in the study were found in genes that are already known to be involved in other cancers and diseases – to use the crime analogy again, they are already in the ‘suspect database’.

These SNPs could therefore be vital clues to potential new treatment targets in prostate cancer. For example:

• One SNP was found in a gene called ZBTB38, which is involved in controlling cell death, a process that cancer cells manage to dodge. It has also been associated with height. This is interesting because previous studies have linked being tall with increased risk of prostate cancer. Could ZBTB38 be the missing link between height and prostate cancer risk?
• Another SNP was found in a gene called TERT. Although this link was already known, this study showed a stronger link than previously thought. TERT has been linked with other cancers including lung, bladder and testicular cancer. It is involved in protecting the ends of chromosomes, and several studies have linked shortened chromosomes to increased cancer risk. Also interesting, the SNP found in this study is in a different region of the gene from those linked in other cancers – this suggests it could be unique to prostate cancer. The researchers also found a link between this SNP and increased PSA levels, which can be raised in men with prostate cancer. What (if any) role does TERT have in raising PSA levels?

The investigation continues

These and other questions are yet to be answered, but with continuing research, scientists are adding to an ever-growing case file against prostate cancer.

Prostate cancer is the most common cancer in men in the UK. Each year, around 10,000 men in the UK die from the disease. Clearly we need to do all we can to reduce the disease’s burden.

The ultimate aim is to be able to assess each man’s individual risk of prostate cancer using information from research like that outlined above. This is already possible to some extent for breast and ovarian cancer, and with continued support from the public we hope to do the same for prostate cancer soon.

Oliver Childs