When her gynecologist recommended genetic testing, Mai Tran was reluctant.
“I didn’t really want to do it,” recalled Tran, who had just turned 21 and was living in New York City, “but she kept on emailing me about it and was really adamant that I do it.”
Tran知道由于她的家族史，她的母亲在患有乳腺癌的风险升高 - 她的母亲死于这种疾病，患有母亲阿姨被诊断并幸存下来。鉴于这一点，她计划跟随standard recommendations在早期开始乳腺癌筛查。
But she feared that if the testing her doctor was suggesting revealed a genetic variation known to cause breast cancer, she would have to decide whether to have her breasts surgically removed. That was a decision she was not ready to make.
Doctors are increasingly testing people’s genes for signs of hereditary risks for cancer, saidDr. Allison Kurian, a medical oncologist and the director of the Women’s Clinical Cancer Genetics Program at Stanford University. If the tests find a genetic variation known to cause cancer, treatments or preventive measures may be recommended to prevent the disease, she said.
But the trend can unsettle patients like Tran, sometimes unnecessarily, because many genetic findings are ambiguous, leaving doctors uncertain about whether a particular variant is truly dangerous.
2012年出现的多基因面板测试以及这些面板中覆盖的基因数量以来，膨胀后tests that include more than 80 genes associated with cancercommonly available.
然而，在测试更多基因的情况下，寻找不确定的结果的可能性 - 对于患者来说，可能对医生解释的医生来说令人困惑。一种study by Kurianshowed that multiple-gene screening was 10 times more likely to find inconclusive results than a test that examines only two genes,BRCA1和BRCA2，长期与乳腺癌和卵巢癌的风险较高。
在医学界中的不确定结果是一种不确定意义或vus的变种。它可能是基因的无害变异 - 或与癌症联系的一个。
Detecting such variations is common.一种reviewshowed the percentage of patients who learn they have a VUS after multiple-gene panel testing varied in studies from 20% to 40%.
Farmer has seen patients change their minds when she informs them of this reality. “That patient that thought they wanted everything [tested] might then kind of scale back what they were looking for.”
Kurian said patients can be tested for all the cancer genes available as long as they understand that the analysis of many genes will likely not be informative. Several years later, if more evidence accumulates for a particular gene, those results may inform medical decisions.
People who belong to racial minority groups have特别高的可能性根据斯坦福研究人员在内的研究，因为大多数基因在白人中首先在白人中排列，往往在白人中首先进行测序，因为斯坦福等研究人员在包括Kurian等研究人员，他们也倾向于更好地获得测试。它表明，在具有多基因面板测试的种族各种人群中，超过三分之一的人没有白人的vus结果，而四分之一是白人的。
Testing revealed that Tran, who is Vietnamese, had a VUS in a gene associated with林奇综合征, a hereditary condition that increases the risk of developing colon cancer, uterine cancer and other cancers. The genetic counselor explained the VUS was inconclusive and should not be used to inform medical decisions.
一种genetic variant found in testing can be classified — in decreasing severity — as “pathogenic,” “likely pathogenic,” “VUS,” “likely benign” or “benign,” andstudies have shownthat commercial laboratories and companies sometimes disagree on how to classify a variant.
The consensus among experts is not to make medical decisions, such as whether to have surgery, based on a VUS becauseit often turns out to be benign随着更多的研究，越来越多地测试了更多的人。
“I’ve actually seen this a number of times, and it’s a very real concern,” said肯南奥尔博士, a clinical cancer geneticist and the director of the Center for Cancer Prevention and Wellness at the Icahn School of Medicine at Mount Sinai in New York City.
研究人员最近发现证据that doctors may be inappropriately recommending surgery based on a VUS. The results were presented virtually at the 2020 American Society of Clinical Oncology annual meeting and have not yet been published in a peer-reviewed journal.
It is not just the procedure that causes problems, explained the researcher who led the study,苏珊博士多克斯博士, a medical oncologist and executive director of the Basser Center for BRCA at Penn Medicine’s Abramson Cancer Center. Women who have their ovaries taken out before menopause start menopause early, which raises their risk of developing health problems such as osteoporosis and heart disease.
专家说他们甲型肝炎患者学习e a VUS or receive conflicting results should see a provider with expertise in genetics, such as a genetic counselor or clinical cancer geneticist, especially if surgery is being recommended.
“This has been a two-plus-year struggle for me,” said Marcus. “I felt very alone, and nobody could give me any answers.”
This story can be republished for free (细节).
Kaiser Health News
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