UCSF-led team discovers possible cancer 'susceptibility' gene

A UCSF-led team has identified a common variant of a gene known as Aurora2 that may increase susceptibility to cancer development. The finding provides one of the first examples of an elusive type of "low penetrance" tumor susceptibility gene in humans.

The results, reported in the July 27 on-line version of Nature Genetics, support the emerging viewpoint that common variant forms of some genes can contribute to cancer susceptibility, particularly when a number of these variant genes are co-inherited and therefore can act in concert.

Traditionally, advances in understanding cancer predisposition have involved discoveries of rare, inherited, full-fledged genetic mutations that dramatically increase the risk of cancer, such as the brca1 and brca2 genes in breast cancer. But scientists have come to recognize that such "high penetrance" genes account for only 5-10 percent of cancers.

Evidence from mouse models and human epidemiologic studies suggests that susceptibility to most cancers results from numerous low penetrance polymorphisms acting together to disrupt a cell's regulatory controls. In themselves, these subtle variations are not harmful. A mouse or human that inherits a mildly more active form of a certain regulatory gene such as myc or ras won't necessarily have a problem. But the evidence suggests that if either inherits a number of overly active regulatory genes that act synergistically, cancer is more likely to develop.

"It's like the components of a lock it's the combination of these polymorphisms that makes a substantial difference in susceptibility," says senior author Allan Balmain, PhD, UCSF professor of biochemistry and Barbara Bass Bakar Endowed Chair in Cancer Genetics at the UCSF Comprehensive Cancer Center. "We're trying to identify the components of the lock. The Aurora2 story is the first component we've identified."

While much evidence has suggested that cancer susceptibility genes exist in humans, id

Contact: Jennifer OBrien
University of California - San Francisco

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