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Scientists move in on genes conferring susceptibility, resistance to cancer

sh exposure to cytotoxic therapeutic drugs," says Balmain.

Moreover, he says, "If we could predict who has which variants of these genes, we could proactively assess people for the likelihood of susceptibility to cancer and recurrent tumors through blood tests."

The researchers conducted their study in two species of mice - one, known as Mus musculus, has been inbred over many generations in the laboratory, so that all of the animals in any one strain are genetically identical; the second species, known as Mus spretus, is, by nature, highly resistant to tumor development in several organs, such as the lung, skin, liver and colon.

The investigators made hybrids between these two types of mice to track the genes responsible for making the spretus mice resistant to cancer. They exposed the two species to cancer-causing agents, and then used genetic mapping techniques to find regions of the genome that influence the number of benign tumors that formed, whether they progressed to malignancy, and at what rate.

The investigators identified ten genetic regions that significantly influenced tumor development. They also discovered a specific combination of a subset of the resistance-associated regions that was significantly associated with increased survival time once a malignant tumor developed.

"The study shows that some of these variants are very potent at preventing cancer," says Balmain. Most likely, he says, the genes involved control different aspects of the process leading to cancer, such as the growth rate of cells and the ability of tumors to grow blood vessels that will then provide them with the nutrients they need to grow.

Notably, the UCSF researchers have discovered that some of the genes that control the susceptibility to skin cancer are in the same positions in the mouse genome as those associated with susceptibility to colon and lung cancer. And this suggests, says Balmain, that there may be some "mas
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
3-Apr-2000


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