SAN FRANCISCO, July 5 (Xinhua) -- Researchers working on a study led by Stanford University have assigned levels of risk to 25 mutations associated with breast and ovarian cancer, and the results may be helpful in guiding treatment and screening recommendations.
In the largest study of its kind, the researchers have analyzed the genetic test results, family histories and disease status of 95,561 women who underwent genetic testing for 25 mutations associated with the development of breast and ovarian cancer. Some of the women had cancer; many did not. Seven percent of the women carried at least one of the mutations.
The researchers at the Stanford School of Medicine and Fox Chase Cancer Center in Philadelphia hope the study is the first step to providing much-needed clarity to women and their physicians as they struggle to interpret the results of genetic testing. It may also help guideline-making organizations such as the American Cancer Society recommend when additional or more-frequent screening tests might be appropriate.
Increasingly, women who are tested for a panel of cancer-associated mutations are given a mixed bag of results. Advances in deoxyribonucleic acid (DNA) sequencing have made it quicker, easier and cheaper to identify mutations in an ever-growing panel of cancer-associated genes. With the exception of a few well-studied mutations such as BRCA1 and BRCA2, however, the exact effect of most of these remains murky because few large-scale studies have been completed.
The researchers assessed the mutation status of the women who chose to have their genome tested by Myriad Genetics for the presence of 25 cancer-associated mutations between September 2013 and September 2016, then matched the women according to their ages, ethnicity and family history of cancer to assign a relative risk of developing cancer to each of the mutations. They found that eight of the mutations were positively associated with the development of breast cancer, and 11 were positively associated with ovarian cancer.
Increased cancer risk for women carrying the mutations ranged from two to 40 times that of a woman without the mutations.
"This large sample size provided a reliable data set on real people," said Michael Hall, associate professor of clinical genetics at the Fox Chase Cancer Center and senior author of the study published online in JCO Precision Oncology. "This is a significant advantage as we work to identify the strength of association between mutation and risk."
In many cases, the findings dovetailed with what had already been surmised from smaller studies. But there were some surprises. One mutation assumed to increase a woman's risk of breast cancer was shown to instead increase the likelihood of ovarian cancer. Three other mutations thought to increase the risk of breast cancer seem instead to have little effect.
"One surprising finding was the association of an increased ovarian cancer risk with mutations in a gene called ATM," Allison Kurian, associate professor of medicine and of health research and policy at Stanford, was quoted as saying in a news release. "Although this risk was relatively small numerically, it was statistically significant, and to our knowledge it had not previously been published. Additional studies will be important to determine the robustness and clinical relevance of this finding, and to expand the evidence base that we use to counsel our patients."
