Ovarian Cancer Genetic Marker
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By Rabiya S. Tuma

Marker of Risk

Researchers uncover a new type of genetic marker

By Rabiya S. Tuma

Following a hunch, researchers have discovered that a known genetic change increases a woman’s risk of ovarian cancer—a finding that may help explain why the disease runs in some families. What’s more, the newly discovered marker of risk is unlike previously identified genetic risk factors, and scientists predict that similar genetic changes may be linked to other cancers.

A cross-sectional CT scan shows ovarian cancer in blue.Doctors have had little success diagnosing ovarian cancer early or identifying women at risk for the disease. With this need in mind, Joanne Weidhaas, a radiation oncologist at Yale University School of Medicine in New Haven, Conn., investigated genetic variations in the KRAS gene. Changes in KRAS are associated with many types of solid tumors, and one alteration in particular, called KRAS-variant, has been linked to poor survival.

When Weidhaas checked the DNA from 157 women with ovarian cancer, she found that 27 percent of the women carried the KRAS-variant, compared with just 18 percent of the general population. Weidhaas identified a similar percentage of women with the KRAS-variant in two additional groups of ovarian cancer patients. Additionally, she found the KRAS-variant in 61 percent of women with ovarian cancer who had a family history but lacked mutations in the BRCA1 and BRCA2 genes, which are known risk factors for the disease.

Based on this data, Weidhaas is convinced that the KRAS-variant promotes ovarian cancer in those high-risk families. “With those proportions of women, it is virtually impossible [the correlation] would be by chance,” she says.

Anil Sood, an oncologist and ovarian cancer expert at the University of Texas M. D. Anderson Cancer Center in Houston, agrees. But he thinks the most exciting aspect of the discovery is that it is a novel type of genetic risk factor. While other genetic risk factors disrupt a key protein directly, the KRAS-variant blocks binding of a small piece of RNA—a type of genetic material—that controls how much KRAS protein is made. “This suggests we may find similar changes in other genes that would explain susceptibility to many cancers,” he says.

Knowing how the KRAS-variant alters the production of KRAS proteins may also help researchers develop effective therapies for a variety of cancers. “We haven’t been very successful targeting KRAS protein in the past,” Sood says.

Weidhaas, who published her findings in the Aug. 15 Cancer Research, says that the novelty of the marker is important for cancer research in general. But in the near term, the KRAS-variant may have a role in the risk assessment of high-risk women with a family history of ovarian cancer. “It won’t change how they are screened at this point, but it could give someone some peace of mind if they don’t have it,” Weidhaas says.

(image: © Medical Body Scans / Photo Researchers Inc.)