A Tiny Variation Predicts Cancer Outcomes
Ovarian cancer patients’ chance of survival and response to treatment can be predicted by a tiny genetic variation, according to new study findings.
The research was published in the journal Oncogene. The results give researchers a new understanding into the biology of a new class of cancer marker and could result in a genetic test may help guide the treatment of women with ovarian cancer.
"This gives us a way to identify which women are at highest risk for resistance to platinum chemotherapy, the standard treatment for ovarian cancer, and helps identify ovarian cancer patients with the worst outcomes," said Joanne Weidhaas, associate professor of therapeutic radiology and senior author of the study in a statement released Monday. "There just aren't many inherited gene variants than can do that."
Researchers identified the biomarker to be a variant of the well-known KRAS oncogene, and women who possess the biomarker are three times more resistant to the standard platinum chemotherapy than women without the variant.
The variant, which helps regulate destruction of damaged cells, is found in about 25 percent of newly diagnosed ovarian cancer patients, and in about 12 to 15 percent of Caucasians and six percent of African Americans. The study also finds that postmenopausal women with the gene variation are significantly more likely to die from ovarian cancer.
Scientists are intrigued by this biomarker because it is a functional variant located in the section of DNA that does not code for proteins, but instead disrupts how microRNA controls gene expression.
"This is a new paradigm," Weidhaas said. The KRAS variant is special its mutation is an essential step in the development of many cancers, and is located in an area in DNA that has only recently been explored. “It is the one of the few inherited change in DNA that can predict the risk of getting cancer and cancer biology… so what looks like different types of cancer tumors, as long as they have the variant, are all pretty similar and can be treated accordingly.”
Furthermore, researchers were able to block the variant to significantly reduce the growth of ovarian cancer cells, and suggest that targeting the variant site may someday treat cancer in patients.
Researchers have also found that this variant of the KRAS gene is associated with an increased risk of developing breast cancer and lung cancer. In other research the variant has been associated with poor outcome in colon, head and neck cancers.
The National Cancer Institute (NCI) estimated that 21,990 women will be diagnosed with and 15,460 women will die of ovarian cancer in 2011 and causes more deaths than any other reproductive cancer, according to statistics from National Center for Health Statistics (NCHS).
While effective alternatives to chemotherapy are still unavailable for women with ovarian cancer and this variant, drugs in development which target the KRAS gene and similar pathways are shown great promise, Weidhaas said.
Weidhaas is also a co-founder of a company which possesses licensed intellectual property from Yale that has developed a diagnostic test based on the Kras-variant.