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February 15, 2007

SickKids researchers discover predictive marker for early onset cancer in some cancer-prone families

TORONTO - Researchers at The Hospital for Sick Children (SickKids) have found that the rate of shortening of the ends of chromosomes in the white blood cells in people with Li-Fraumeni syndrome can predict the time of the onset of tumour development. This research is reported in the February 15 issue of the journal Cancer Research.

Li-Fraumeni syndrome is a familial cancer syndrome which predisposes primarily children and young adults to develop cancer. This disease affects 1 in 10 000 people and those diagnosed carry an almost 50 per cent chance of developing cancer before the age of 20. Even more dramatically, almost all women with Li-Fraumeni syndrome will develop cancer in their lifetime, 55 per cent of them developing breast cancer. A major question has always been when.

“Several years ago, we and others discovered that people with Li-Fraumeni syndrome had inherited a mutation of the p53 gene, and this resulted in dramatic occurrences of cancer. We also noticed that cancers were developing at younger and younger ages with each successive generation in each family,” said Dr. David Malkin, the study’s principal investigator, staff oncologist and co-director of the Cancer Genetics Program, senior scientist in Genetics & Genome Biology at SickKids, professor of Paediatrics at the University of Toronto. “We wondered why different members of the family develop cancer at different times, if each affected family member carried the identical specific mutation in the p53 gene.”

Each time a normal cell divides, its chromosomes, which contain the cell’s genetic material, divide as well and their ends, known as telomeres, will shorten slightly. After many generations of cell divisions, the chromosomes eventually shorten to a point where the telomeres do not work properly and the cell’s genetic material becomes unstable.

“We hypothesize that people with this syndrome are passing on shorter telomeres and more genomic instability with each generation,” said Malkin.

While this instability means that patients with Li-Fraumeni will get cancer younger, it also means that clinicians may now have a tool to help predict at what age these patients will develop cancer. Telomere length may be used as a prognostic marker to help to predict when it is most appropriate to begin cancer screening in these patients.

“This finding means that if a patient has a cancer predisposition syndrome, you can time the prevention options; when the development of cancer occurs in this patient becomes less of a mystery,” said Dr. Uri Tabori, study lead author, associate scientist, Genetics and Genomic Biology, staff oncologist, principal investigator in the Arthur and Sonia Labatt Brain Tumour Research Centre and assistant professor of Paediatrics at the University of Toronto. “The most important aspect of this discovery is the concept, and the impact it will have on the management and treatment of all patients with cancer predisposition syndromes.”

“While we do not yet know why cancer develops, we now, at least for patients with this syndrome, have a better idea of when they will develop it.”

Other members of the research team included Sonia Nanda, Harriet Druker and Jodi Lees, all from SickKids. This research was supported by the National Cancer Institute of Canada with funds from the Canadian Cancer Society, and SickKids Foundation.

The Hospital for Sick Children (SickKids), affiliated with the University of Toronto, is Canada’s most research-intensive hospital and the largest centre dedicated to improving children’s health in the country. As innovators in child health, SickKids improves the health of children by integrating care, research and teaching. Our mission is to provide the best in complex and specialized care by creating scientific and clinical advancements, sharing our knowledge and expertise and championing the development of an accessible, comprehensive and sustainable child health system. For more information, please visit www.sickkids.ca. SickKids is committed to healthier children for a better world.

For more information, please contact:

Janice Nicholson
Public Affairs
The Hospital for Sick Children
Phone: 416-813-6684
Fax: 416-813-5328
email: janice.nicholson@sickkids.ca