Racial Differences in Response to Bowel Cancer Genetic Risk Factor
1 April 2008
IGMM scientists have for the first time discovered that people with the same cancer susceptibility genes respond differently depending on their race. Their results are published in Nature Genetics.
The team from the University of Edinburgh has shown that a genetic marker is associated with an increased the risk of colon cancer in Europeans, but not in the Japanese population. But this genetic variant was associated with a similar risk of rectal cancer in both populations.
While dietary differences are already well known to be important, this discovery shows for the first time that genetic factors might explain some of the differences in bowel cancer risk between populations.
This is one in a series of Cancer Research UK funded studies searching for bowel cancer susceptibility genes. The international collaborative project has the long term aim to find a set of genetic markers that could be used to identify subgroups of the population with an increased risk of bowel cancer.
Lead author, Cancer Research UK's Professor Malcolm Dunlop based at the Institute of Genetics and Molecular Medicine at the University of Edinburgh, said: "This is the first time that a race-specific effect has been found for a genetic marker. It's an important step forward in our knowledge of the causes of bowel cancer, bringing us ever closer to a genetic test for those at high risk of the disease.
"It's important to catch bowel cancer at an early stage when it's more likely to be treated successfully."
Prof Dunlop and his team looked at the complete genetic make up of over 33,000 people in seven different countries.
In a parallel study, also published in Nature Genetics, a team of researchers led by Professor Richard Houlston based at the Institute of Cancer Research, Professor Ian Tomlinson at Cancer Research UK's London Research Institute along with Professor Dunlop and Professor Campbell in Edinburgh found two new gene variants that increase the risk of bowel cancer.
Cancer Research UK's director of cancer information, Dr Lesley Walker, said: "Our understanding of the causes of bowel cancer is quickly increasing. We can now begin to explain the some of the difference in rates of the disease between populations through specific genes.
"This international collaboration has helped us appreciate the complexity of the genetics behind bowel cancer. This collaboration will continue to bring knowledge that will eventually allow us to test people with a family history of the disease, catching cancer earlier in those who are at the highest risk or preventing it all together."
Related Links
The Scotsman: Scientists find Ethnic Link to Bowel Cancer
BBC News: Racial Clues in Bowel Cancer Find
Genetics of
Inflammatory Bowel Diseases
14 May 2008
A UK multi-centre study published in the journal Nature Genetics has identified a new gene for ulcerative colitis - one of the first to be confirmed for this condition - and in a decisive breakthrough establishes a series of genetic links between the inflammatory bowel diseases (IBD), ulcerative colitis and Crohn's disease. Since these are diseases of young people involving debilitating pain, embarrassing symptoms, a high risk of surgery and an increased risk of cancer, the researchers hope that these findings will translate directly to safe effective therapeutic strategies.
The multi-centre UK IBD Genetics team led jointly by Professor Jack Satsangi of IGMM at the University of Edinburgh, Professor Chris Mathew of King's College London, and Dr Miles Parkes of Addenbrooke's Hospital, Cambridge found the new ulcerative colitis gene, ECM1, and showed that five other genes, which were previously shown to be involved in Crohn's disease, also predispose to ulcerative colitis.
Professor Satsangi explains, "This new study sheds more light on the underlying inherited factors that place people at risk of developing ulcerative colitis, and with the discovery of the ECM1 gene involvement highlights the role of gut barrier function."
Funded by the National Association for Colitis and Crohn's disease (NACC), the study involved over 3,000 UK patients with ulcerative colitis and applied new technologies for human genome scanning. As such it is the most detailed investigation of ulcerative colitis genetics in the world literature.
Three of the findings will be of great impact on the direction of inflammatory bowel research. Firstly, the new UC gene identified in this study, ECM1 encodes a protein which is implicated in maintaining the barrier function of the gut wall, and the finding suggests that an inherited defect in the gut wall - a leaky gut - may predispose to ulcerative colitis. Secondly, the five genes which the investigators show to predispose to either ulcerative colitis or Crohn's disease are involved in aspects of regulation of the immune system. Finally, several genes which this team have previously shown to be important determinants in Crohn's disease are not implicated in ulcerative colitis
- of these Crohn's disease-specific determinants, NOD2/CARD15, ATG16L1 and IRGM all affect the body's ability to identify and deal with gut bacteria.
Professor Satsangi explains, "The results are of real importance to patients, physicians as well as scientists. The insights gained from these genetic discoveries may lead to new treatment strategies, for
individual patients. Moreover, for the first time, we are finding scientific evidence for the relationship between Crohn's disease and ulcerative colitis, sharing some but not all susceptibility genes. These
findings provide a springboard for further studies of IBD genetics, and for the mechanisms whereby environmental factors interact with these
genetic determinants. We hope these findings will translate directly to safe effective therapeutic strategies, by identifying new drug targets."
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