Abstract
Scientists at the Stanford University School of Medicine report that as many as 10% of women with a personal or family history of breast or ovarian cancer have at least one genetic mutation and that, if known, this information would prompt their doctors to recommend changes in their healthcare.
The women in the Stanford research project did not have mutations in BRCA1 or BRCA2, but they did have mutations in other cancer-associated genes. The study (“Clinical Evaluation of a Multiple-Gene Sequencing Panel for Hereditary Cancer Risk Assessment”) appears in the Journal of Clinical Oncology and was conducted using multiple-gene panel technology to sequence a few possible genetic abnormalities selected by researchers based on what is known about a disease. Although such panels are becoming widely clinically available, it's not been clear whether their use can help patients or affect medical recommendations.
“Although whole-genome sequencing can clearly be useful under the right conditions, it may be premature to consider doing on everyone,” said James Ford, M.D., who directs Stanford's Clinical Cancer Genetics Program. “Gene panels offer a middle ground between sequencing just a single gene like BRCA1 that we are certain is involved in disease risk, and sequencing every gene in the genome. It's a focused approach that should allow us to capture the most relevant information.”
Whole-genome sequencing can be potentially life-saving, but the challenges involved in sequencing the billions of nucleotides that make up all of a person's DNA and then translating the results into clinical care recommendations are significant, continued Dr. Ford. The study on gene panels, which allow researchers to learn the sequences of several genes simultaneously from a single blood sample, showed that:
“Among women testing negative for BRCA1/2 mutations, multiple-gene sequencing identified 16 potentially pathogenic mutations in other genes (11.4% 95% CI, 7.0% to 17.7%), of which 15 (10.6%; 95% CI, 6.5% to 16.9%) prompted consideration of a change in care, enabling early detection of a precancerous colon polyp,” wrote the investigators. “Additional studies are required to quantify the penetrance of identified mutations and determine clinical utility. However, these results suggest that multiple-gene sequencing may benefit appropriately selected patients.”
“This study indicates that using gene panels to screen for potentially harmful variants can be clinically useful in certain groups of patients,” said Allison Kurian, M.D., assistant professor of medicine and associate director of the Clincial Cancer Genetics Program. “It also shows that patients, some of whom had given blood samples for research as many as 10 years earlier, are willing and interested to receive this type of follow-up information and to incorporate it into their healthcare plans.”
Eleven of the 14 women in the study were reachable by telephone, and 10 accepted a follow-up appointment with a genetic counselor and an oncologist to discuss the new findings. One woman, with a history of both breast and endometrial cancer, learned she had a mutation that causes Lynch syndrome, a condition that increases the risk of many kinds of cancer. As a result, she had her ovaries removed and underwent a colonoscopy, which identified an early precancerous polyp for removal.