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.”


This story also ran onThe Washington Post。有可能republished for free.

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%.

“小组有人命令越大,我们就越有可能找到一个甚至多重变种的不确定变种,”在我的基因咨询公司遗传临床行动主任,康涅狄格州的康涅狄格州的康复咨询工具总监,提供在线遗传咨询工具。

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.

Kurian表示,“这是错误的”进行测试。“但需要由各方适当处理。”

在2018年秋季,从未听说过VUS,Tran在最全面的筛查中定位:基因面板,当时评估67种癌症类型的基因。

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.

虽然TRAN不居住在VUS上,但测试过程本身造成了情绪动荡。“我真的是为了我的医生而不是自己的测试,”Tran说。“如果我能选择,我就不会这样做。”但其他患者通过不确定的结果更加不安。“VUS是可怕的,因为它是一个克拉普斯郡,”加利福尼亚州比佛利山庄的Logan Marcus说。她在BRCA1中有一个罕见的变体,即一个遗传检测公司所说的“可能致病”,另一个说是“VUS”。

用于最新消息和更新

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。

然而,没有遗传学培训的医生往往不会遵循这种建议。

“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.

关于他们对多基因面板检测的经验进行了调查了7,000多名妇女,以及在与卵巢癌相关的基因中有VUS的体验,其中15%的卵巢和输卵管被移除。这些妇女不需要手术,因为专家表示,不应用来制造医学决策。此外,许多这些女性没有卵巢癌的家族史,并且没有达到更年期,但80%的人报告说,他们的医生推荐手术或作为一种选择讨论它。

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.

该研究还表明,医生常常推荐手术,即使对于没有与卵巢癌未与卵巢癌有关的基因的改变的女性,Domchek表示,缺乏在遗传学培训的医生经常误解这些结果。

在另一个study,农民和她的同事描述了实例,当医疗保健提供者命令错误的遗传测试或误解结果时。其他研究人员发现that nearly half of 100 surveyed doctors were unable to correctly define a VUS.

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.

在寻求癌症的癌症和遗传辅导员的建议之后,马库斯计划有多个亲属,并计划有一种双重乳房切除术,以防止乳腺癌,并给予她的安心,但她不确定她是否会被移除卵巢癌以防止卵巢癌。在39岁时,她还没有孩子。

“This has been a two-plus-year struggle for me,” said Marcus. “I felt very alone, and nobody could give me any answers.”

Kaiser Health News(KHN) is a national health policy news service. It is an editorially independent program of theHenry J. Kaiser Family Foundationwhich is not affiliated with Kaiser Permanente.

使用我们的内容

This story can be republished for free (细节).

by

Christina Bennett

Kaiser Health News

Kaiser Health News是一个涵盖健康问题的非营利新闻服务。它是凯撒族家庭基金会的一位担宗独立计划,这不是凯撒永久的隶属关系。