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Shortening chromosomes cause for earlier cancer onset in families with rare syndrome

PHILADELPHIA -- In families with a high incidence of Li-Fraumeni syndrome, the ends of individuals chromosomes act somewhat like a lit fuse, according to researchers at The Hospital for Sick Children in Toronto. Their findings detail how telomeres, the ends of the chromosomes, shorten with every successive generation, leading to more severe cancers at an earlier age.

Their results, published in the February 15 issue of the journal Cancer Research, could represent the first biological marker for clinical monitoring in families with Li-Fraumeni syndrome, and could shed light on the important area of aging in cancer research

"We have known since 1990 that Li-Fraumeni was associated with inheritance of a mutated form of the p53 tumor suppressor gene, but we also noticed each generation developed cancer earlier than the preceding generation," said David Malkin, M.D., the studys principal investigator, and co-director of the Cancer Genetics Program at The Hospital for Sick Children at the University of Toronto. "By studying blood samples taken from families in which members have Li-Fraumeni, we have discovered that telomeres become shorter in each generation of disease carriers, leading to a genetic instability that primes them for progressively earlier cancers."

First discovered in 1969, Li-Fraumeni syndrome is an inherited disorder that causes a wide spectrum of cancers, including breast, brain, bone and soft tissue cancers. To develop the disorder, a child only needs to receive one mutated p53 gene from one parent. Typically, the disease causes cancers relatively early in life and can strike numerous times, in differing forms, throughout a patients life. According to Malkin, the disease afflicts between one in 10,000 to 40,000 people, but the exact number cannot be accurately determined since the random nature of the cancers makes accurate diagnosis of Li-Fraumeni difficult.

A major mystery of the disease, according to Malk
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Contact: Greg Lester
lester@aacr.org
267-646-0554
American Association for Cancer Research
15-Feb-2007


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