基因检测结果呈阴性可能是"虚假的安慰"

Consumer genetic tests could be giving false reassurance to those at heightened risk of cancers, according to findings presented at an international conference last week.

上周一次国际会议上公布的研究结果显示，消费者基因测试可能会给那些癌症风险更高的人带来虚假的安慰。

The study, by clinical genetic testing company Invitae, revealed that tests for breast and bowel cancer risk by direct-to-consumer companies such as 23andMe give negative results to the vast majority of those carrying DNA mutations in the genes under investigation.

这项由临床基因检测公司Invitae开展的研究显示，23andMe等直接面向消费者的公司对乳腺癌和肠癌风险的检测显示，绝大多数携带受测基因DNA突变的人检测结果都是阴性的。

"These tests should not be taken at face value at all, whether they are positive or negative," said Edward Esplin from Invitae ahead of the annual meeting of the American Society of Human Genetics in Houston, Texas.

在美国人类遗传学学会于德克萨斯州休斯顿召开年度会议之前，来自Invitae的爱德华·埃斯普林说：“这些检测不应该只看表面价值，无论检测结果是阳性还是阴性。”

"The data really underscores that there needs to be increased awareness that results from this type of screening may not be wrong but they're woefully incomplete."

“研究数据强调的是，人们需要认识到，这种检测的结果可能不会是错误的，但遗憾的是，它们是不完整的。”

The research also showed that those from Asian and African-American backgrounds were more likely to carry mutations that were not designed to be detected by the consumer tests.

这项研究还表明，有亚裔和非洲裔血统的美国人更有可能携带突变基因，而消费者测试无法检测到这些突变基因。

The research focused on DNA-based tests relating to breast, ovarian and bowel cancer that were recently approved by the US Food and Drug Administration.

这项研究的重点是美国食品和药物管理局（FDA）最近批准的与乳腺癌、卵巢癌和肠癌相关的DNA检测。

The tests operate by a subject sending a DNA swab in the post for analysis and then receiving results with information about how their genetics could influence their health.

测试是这样进行的：受试者寄送DNA样本用于分析，然后收到有关基因对健康影响的检测结果。

In the case of breast and ovarian cancer, the FDA has approved a screening test for three specific mutations on the BRCA1 and BRCA2 genes, which are most common in people of Ashkenazi Jewish heritage. However, these mutations are rare in people from other backgrounds.

就乳腺癌和卵巢癌而言，FDA已经批准了一项针对BRCA1和BRCA2基因三种特定突变的筛查测试，这两种突变在德系犹太人中最为常见。然而，这些突变在其他血统的人身上很少见。

Similarly, for bowel cancer, 23andMe offers FDA-authorised tests for two mutations, which are most common among individuals of northern European ancestry. The company explains the limitations of these tests to consumers and on its website.

类似地，对于肠癌，23andMe公司提供FDA授权的两种基因突变检测，这在北欧血统的人中最为常见。该公司在其网站上向消费者解释了这些测试的局限性。

Esplin said that despite this, consumers could be wrongly reassured by a negative result.

埃斯普林表示，尽管如此，消费者仍可能被阴性结果错误地打消疑虑。

The study analysed the DNA of 270,806 patients who had been referred by healthcare providers for testing of the MUTYH gene, and 119,328 who had been referred for BRCA1/2 genetic testing.

这项研究分析了270806名被医疗机构推荐进行MUTYH基因检测患者的DNA，以及119328名被推荐进行BRCA1/2基因检测患者的DNA。

It showed that for both tests, the majority of those carrying mutations would not be spotted, which Invitae describes as a "clinical false-negative result".

结果显示，在这两种检测中，大多数携带突变的人都没有被发现，Invitae将其描述为“临床假阴性结果”。

For MUYTH, 40% of individuals with mutations in both copies of their MUTYH genes – consistent with an almost 100% lifetime risk of bowel cancer – had different mutations to those screened for in the FDA-approved test. This figure rose to 100% for those from Asian backgrounds and 75% for African-Americans.

对于MUYTH基因，在携带有两种MUTYH基因拷贝突变的人中，有40%的人的突变与FDA授权检测到的突变不同。这个数字在亚裔美国人中上升到100%，在非洲裔美国人中上升到75%。携带有这两种基因突变的人一生中罹患肠癌的风险几乎是100%。

For BRCA genes, 94% of non-Ashkenazi Jewish individuals and 19% of those of Ashkenazi heritage had a mutation that would be missed. Again, the figures were highest for those of Asian (98%) and African-American (99%) ancestry.

对于BRCA基因，94%的非德系犹太人和19%的德系犹太人携带有可能被遗漏的基因突变。同样，亚裔（98%）和非裔（99%）的比例最高。

"A clinical false-negative result can be incorrectly reassuring, excluding a patient from receiving the preventive care they need based on their risk," he added. "It could be the difference between preventing cancer and developing cancer."

他补充说：“临床假阴性的结果可能是误导性的安慰，使人们不再接受需要基于风险而进行的预防性治疗。人们可能会患上原本可以预防的癌症。”

In response to the findings, 23andMe said in a statement: "The claims made by a competitor that we are returning 'clinical false negatives' is incorrect and a false characterisation of 23andMe's test. Our test is extremely accurate. As part of the FDA authorisation process we've demonstrated over 99% accuracy for the variants we test for in our health product."

针对这些发现，23andMe在一份声明中表示：“竞争对手声称我们正将‘临床假阴性结果’退回是假消息，其对本公司测试的特征描述也是错误的。我们的测试非常准确。作为FDA授权检测过程的一部分，我们已经证明，我们的健康产品基因变异测试准确性超过99%。”

The company said it makes clear to customers that it tests only for certain genetic variants and that customers should not forgo any recommended testing based on 23andMe results. "23andMe is not a diagnostic test," the company said. "If an individual has a family history of cancer or other indications for clinical testing we always recommend consulting a healthcare provider first."

该公司表示，已向客户明确表示，只检测某些基因变异，客户不应放弃任何基于23andMe结果的推荐检测。该公司表示：“这不是诊断测试。如果一个人有癌症家族史或其他临床检测的适应症，我们一直建议首先咨询医疗机构。”

Prof Anneke Lucassen, a clinical geneticist at the University of Southampton, said that, in her experience, non-specialists would be likely to wrongly interpret negative results as an "all-clear".

南安普顿大学临床遗传学家安妮克·卢卡森教授表示，根据她的经验，非专业人士很可能会错误地将阴性结果解读为“没有风险”。

"I do think the 'false-negative' rate is an issue, not necessarily through the companies' fault but through low general awareness," she said. "Most people who come to clinic ask: 'Have I got the gene for breast cancer?' and imagine it's a single test, not that the test involves looking through around 20,000 letters of the genetic code to see if any one of them might be different."

她说：“我确实认为假阴性率是个问题，这不一定是由于公司的失误，而是由于人们的普遍意识不强。大多数来诊所的人会问：‘我有乳腺癌的基因吗？’想象一下，这是一个单一的测试，而不是通过检查大约两万个基因序列编码来判断哪些有所不同。”