For many victims of asbestos-related diseases their main question is ‘why me?’ Having shared life experiences with friends and families who escaped unharmed, why did they draw the deadly short straw that saw them succumb to mesothelioma? New medical research thinks the answer may lie in the genes.
The Genetic Understanding of Asbestos Related Disorders (GUARD) project began in Western Australia in 2007 as a result of the Wittenoom cohort studies. These studies tracked the health of people who lived and worked in the asbestos-mining town of Wittenoom in the north of WA, and provide compelling evidence that genetic factors play a part in determining who will develop the disease.
Geneticist Professor Lyle Palmer is leading the international research team. The former founder of the Centre for Genetic Epidemiology and Biostatistics at the University of Western Australia is now executive director of health studies at the Ontario Institute of Cancer Research (OICR) in Toronto. He has had a long research interest in asbestos-related disease and and says it poses particular problems.
“Humans are not evolved to respond to asbestos. We have no defences against it. It’s not like diabetes, where humans have evolved over millions of years to lay down fat because early hunters-gatherers needed to survive when they might only be able to eat every two or three days.”
Professor Palmer hopes that the discovery of the genetic “switch” for mesothelioma could lead to earlier diagnosis, more effective treatment and perhaps even a cure for the disease.
He points out that finding the genes involved in mesothelioma could also help to fast-track vital research to the clinical trials stage. “What we hope to find are the genes that determine the people who are at high risk of developing the disease and the people who will respond to therapy and, importantly, to better understand the biological processes, the pathways, that lead to cancer,” he says.
The research could also offer fundamental knowledge about the molecular pathways leading to types of cancer. Do changes occur in specific genes, for instance, or throughout large regions of chromosomes?
“We don’t understand the biology of most diseases very well, particularly cancer,” Professor Palmer says. “Cancer is caused by a combination of environment and genetics. Take the genetic markers of the cells that are cancerous and your own genetic make-up and it is those two together that determine risk and the progression of cancer.”
Mesothelioma is unique among cancers in that it has just one known cause: asbestos exposure. Professor Palmer points out that this offers the tantalising possibility that genetic research will produce ground-breaking results.
“With a disease such as breast cancer, for instance, the biology that researchers have to unpack is extremely complex: there are all these exposures across your entire life that could have been the cause (of the cancer), or it could be a combination of several or many factors.
“Even with lung cancer and smoking, we know that smoking causes lung cancer but we still don’t know what it is in tobacco that actually causes cancer. Mesothelioma is a much simpler story. Because we know it has a single cause – asbestos – we have a much clearer picture of the disease and there is already extremely good data about exposure levels and their effects. That raises the question of how the environment interacts with your own genetic make-up.”
Professor Bill Musk, who led the original Wittenoom cohort studies, says clusters of the disease appear within families from the town. “We know that mesothelioma tends to be more conspicuous in some families than others, and the Wittenoom studies were critical to discovering this,” he says.
“The data estimates that if you have a first-degree relative – that is, a father, mother or sibling – with the disease, then your risk is approximately doubled after allowing for (asbestos) exposure.”
Professor Palmer says Wittenoom was a tragedy – but something of a miracle, too. “The amazing thing about Wittenoom is that most people who lived there did not get mesothelioma – and that’s what makes it so interesting for geneticists. The Wittenoom cohort allows us to study a group of sufferers and, alongside them, a group of people who had similar levels of exposure to asbestos but did not develop mesothelioma.”
The GUARD team has taken the DNA of 600 mesothelioma sufferers, many of them from Wittenoom, and matched them with these cancer-free “controls”. In the first research of its kind in the world, Professor Palmer’s team at the Ontario Institute of Cancer Research has scanned the genomes of the 600 sufferers using two million markers for common genes that might cause mesothelioma.
Further research will determine which markers differ from those of people who didn’t develop the disease. “We can also start to look at markers for how severe the disease could be and at what age a person may get it. We want to find out if there are genes that are specific to mesothelioma and if there are genes shared with other cancers. It’s probably it’s a bit of both.”
The data gleaned from the scans will be analysed by an OICR team, including genetic epidemiologists, infomaticians
By Catherine Madden