Gothenburg, Sweden: New research to be presented today (Monday) at the annual conference of the European Society of Human Genetics shows that a cancer patient's genetic ancestry can have a significant effect both on how their disease progresses and their survival. In the largest study of its kind, researchers examined nearly 1,900 specific genetic changes in tumours in order to measure whether certain mutations were more common in patients with different historic geographic origins.
Presenting their results, Dr Yixuan He, Assistant Professor of Epidemiology at the University of Texas University Health Science Center, Houston, Texas, US, explained how she worked with her PhD student, Ms Jiawei Tu, to analyse the genetic sequencing data from over 30,000 patients from two large cancer centres – Dana Farber (Boston. Massachusetts) and MD Anderson (Houston). The data covered five different cancers: breast, colorectal, glioma (the most common type of brain cancer), pancreas, and lung. As well as examining mutations, the researchers also took socioeconomic status and air pollution environmental factors into account to make sure they did not distort the results. They then created a scoring system based on the genetic mutations to try to predict which patients were more likely to die from their cancer, and tested whether combining ancestry information improved the prediction.
Although prediction scoring has been done before, this is the first analysis of its kind to be carried out on such a scale. "Previous studies have been limited to small groups in a single population and in a single tumour,' says Dr He, "and they have often not taken environmental factors or long-term clinical outcomes into account. By broadening the scope of our study, we hoped to able to show the real, measurable impact of genetic ancestry on cancer genomics and clinical outcomes."
Results showed dozens of mutations that were significantly more or less common depending on the patient's ancestry, about half of which can be targeted by existing treatments. The scoring system was able to predict patient survival, particularly so in breast cancer and glioma. When ancestry information was added, the survival prediction became even more accurate, particularly in cancer of the pancreas.
Tumour sequencing is relatively common in modern cancer care, and genetic ancestry can be estimated from those data, so integrating it would not involve additional costs or tests. Environmental factors can also be estimated simply based on where a patient lives. "The challenge of integration would not come from a lack of appropriate technology, but from a workflow that allows the derivation of these important factors from existing routine data collection," Dr He says. "We are currently collaborating with oncologists in the hope of overcoming these barriers."
The researchers now intend to expand their analyses to include other cancers and to incorporate additional environmental factors such as smoking and other pollutants – ideally, working with other groups to replicate their findings in other patient cohorts. Although some of their conclusions were already known, they were also able to identify several new associations, for example the over-representation (enrichment) of a gene involved in the control of cell proliferation (CDK6) in African American breast cancer patients, and the loss of SMAD2, another cell proliferation-controlling gene, in American colorectal cancer patients with an admixed ancestry..
"It was very encouraging to see consistent ancestry-related signals replicated between our two different biobanks despite the geographic and population differences between them. By identifying specific genetic markers linked to ancestry we can pinpoint targetable mutations to help doctors use treatments with better survival outcomes. In validating these signals across different populations, we can ensure that a particular treatment is adapted to and effective across a diverse range of patients," Dr He concludes.
Chair of the conference, Professor Alexandre Reymond, who was not involved in the research, said: "This study shows convincingly the need to assess the disease risks in diverse populations if we are to be able to fully personalise medicine and help the maximum number of patients."
