Discovering the importance of genetics
Train fares, electricity bills, house prices – it feels like everything has become more expensive over the past twenty years. But there’s one bargain that could transform the way we tackle prostate cancer – the cost of gene sequencing.
The first successful attempt to map out all the genes in our DNA cost over £1,000,000,000 in the 1990s; today it would only set you back £1,000. With that progress, we’ve been able to dig much deeper into the importance of our genes.
Nature or nurture
Our genes influence almost all aspects of ourselves. Some of these, like eye colour, are entirely controlled by genes, while others, like height, are influenced by a mix of the genes we inherit from our parents and our environment.
It can be difficult to separate the contribution of genetics from our lifestyle and environment. Fortunately, nature has provided us with a way – twins. By comparing the similarities between identical and non-identical twins, researchers can see what influence our genes have on our lives. Importantly, this helped to reveal just how much our genes affect a man’s risk of prostate cancer.
“Prostate cancer is one of the most heritable cancers,” says Professor Ros Eeles from The Institute of Cancer Research, London. “Our current estimate from twin studies is that genetics may account for over 50 per cent of the risk.”
Professor Eeles is one of the world’s leading experts on prostate cancer genetics, splitting her time between running her own genetics lab and seeing patients in hospital. One of our very first research grants was awarded to her in 1995 towards a machine for her new lab to detect and amplify small amounts of DNA.
“The PCR machine was part of us setting up our lab and it was a very significant contribution at that time. It made a big difference. The charity very much helped us to kickstart our lab, which has enabled us to be a very successful group,” she says.
We have since found three-quarters of the genes discovered to influence the risk of developing prostate cancer.
Over the years, we have continued to support Professor Eeles’ work, particularly looking at the BRCA genes. These genes are most commonly associated with breast cancer, as mutations can massively raise the risk of the disease. Famously, in 2013 Angelina Jolie announced that she’d had a preventative mastectomy based on her genetic profile containing a mutated BRCA gene.
Our research helped to discover that these rare mutations can also increase men’s risk of prostate cancer, particularly at an early age. Although this effect isn’t as strong as in breast cancer, the BRCA genes are the most important genes in prostate cancer and lead to a particularly aggressive disease.
“When we look back through our old data, everyone who had a BRCA2 mutation and was diagnosed with prostate cancer was dead within five years. Now, we’re seeing men with these mutations living longer and that’s hugely inspiring,” says Professor Eeles.
However, there are many other genes that appear to be involved and have variants that are commonly found in the general population. On their own they might only have a subtle effect but the combination of these can make a large impact.
“There are 170 gene variants that have been identified,” Professor Eeles says. “In the mid-90s, we didn’t know how many genes there were to find. We had grossly underestimated – it’s much more complicated than we thought. We now know that it’s a mix of rare gene variants, which lead to a very nasty disease, and variants that are common in the general population.”
Catching it early
A lot of Professor Eeles’ research has focused on men diagnosed at an early age, as it’s more likely that genetics has played a role.
“I was surprised that genetics are so important for prostate cancer. Looking back, I never really thought that my dad having prostate cancer would affect my risk of getting it and it’s a shame that as we shared the same GP that the genetic link was never mentioned until I was told that I had it!” says Kevin Webber, who was diagnosed with advanced prostate cancer fours ago. “At 49, with a wife and three children, I was given perhaps as little as two years to live.”
“I hope that in the future we can find the men at high risk of prostate cancer so they can get tested in time, rather than catching it too late like me. I guess that’ll include my boys too, but I’m confident that new research will mean they won’t need to worry about it.”
Putting into practice
Professor Eeles is starting a new clinic at The Royal Marsden NHS Foundation Trust for men who are likely to have high risk genes. “This will be open to three groups of men: those with a family history of prostate cancer, black men and men with prostate cancer who were either diagnosed before 65 or have a family history,” she says. This means that the team can use the men’s genetic makeup to refer them to different studies, which might influence their treatment or better understand their risk.
The genetic variants can identify men who are at a greater risk of aggressive prostate cancer, helping to improve diagnosis and reduce the overdetection of harmless cancers.
To really understand why these genes are important and how they trigger prostate cancer, Professor Eeles is running a study called PROFILE Family History as part of the London Movember Centre of Excellence. “We have already found the genetic variants that we can test for from the previous studies, so the plan for this study is to do targeted screening in men with family history. We will do a biopsy and MRI of everyone in the study and take a sample so we can do the genetic tests. That means we can match up the gene variants with what you’d see in the MRI and biopsy. The aim is eventually to be able to use gene tests for screening.”
As exciting as this is, it’s just a glimpse into what the future might hold from our understanding of genetics. As Professor Eeles says, “The real impact from genetics research will be seen in the next two to five years.”