基因檢測(cè)結(jié)果呈陰性，就不會(huì)患癌癥嗎？

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.

上周一次國(guó)際會(huì)議上公布的研究結(jié)果顯示，消費(fèi)者基因測(cè)試可能會(huì)給那些癌癥風(fēng)險(xiǎn)更高的人帶來(lái)虛假的安慰。

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.

這項(xiàng)由臨床基因檢測(cè)公司Invitae開(kāi)展的研究顯示，23andMe等直接面向消費(fèi)者的公司對(duì)乳腺癌和腸癌風(fēng)險(xiǎn)的檢測(cè)顯示，絕大多數(shù)攜帶受測(cè)基因DNA突變的人檢測(cè)結(jié)果都是陰性的。

“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.

在美國(guó)人類遺傳學(xué)學(xué)會(huì)于德克薩斯州休斯頓召開(kāi)年度會(huì)議之前，來(lái)自Invitae的愛(ài)德華·埃斯普林說(shuō)：“這些檢測(cè)不應(yīng)該只看表面價(jià)值，無(wú)論檢測(cè)結(jié)果是陽(yáng)性還是陰性。”

“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.”

“研究數(shù)據(jù)強(qiáng)調(diào)的是，人們需要認(rèn)識(shí)到，這種檢測(cè)的結(jié)果可能不會(huì)是錯(cuò)誤的，但遺憾的是，它們是不完整的。”

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.

這項(xiàng)研究還表明，有亞裔和非洲裔血統(tǒng)的美國(guó)人更有可能攜帶突變基因，而消費(fèi)者測(cè)試無(wú)法檢測(cè)到這些突變基因。

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.

這項(xiàng)研究的重點(diǎn)是美國(guó)食品和藥物管理局(FDA)最近批準(zhǔn)的與乳腺癌、卵巢癌和腸癌相關(guān)的DNA檢測(cè)。

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.

測(cè)試是這樣進(jìn)行的：受試者寄送DNA樣本用于分析，然后收到有關(guān)基因?qū)】涤绊懙臋z測(cè)結(jié)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，F(xiàn)DA已經(jīng)批準(zhǔn)了一項(xiàng)針對(duì)BRCA1和BRCA2基因三種特定突變的篩查測(cè)試，這兩種突變?cè)诘孪氮q太人中最為常見(jiàn)。然而，這些突變?cè)谄渌y(tǒng)的人身上很少見(jiàn)。

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.

類似地，對(duì)于腸癌，23andMe公司提供FDA授權(quán)的兩種基因突變檢測(cè)，這在北歐血統(tǒng)的人中最為常見(jiàn)。該公司在其網(wǎng)站上向消費(fèi)者解釋了這些測(cè)試的局限性。

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

埃斯普林表示，盡管如此，消費(fèi)者仍可能被陰性結(jié)果錯(cuò)誤地打消疑慮。

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.

這項(xiàng)研究分析了270806名被醫(yī)療機(jī)構(gòu)推薦進(jìn)行MUTYH基因檢測(cè)患者的DNA，以及119328名被推薦進(jìn)行BRCA1/2基因檢測(cè)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”.

結(jié)果顯示，在這兩種檢測(cè)中，大多數(shù)攜帶突變的人都沒(méi)有被發(fā)現(xiàn)，Invitae將其描述為“臨床假陰性結(jié)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.

對(duì)于MUYTH基因，在攜帶有兩種MUTYH基因拷貝突變的人中，有40%的人的突變與FDA授權(quán)檢測(cè)到的突變不同。這個(gè)數(shù)字在亞裔美國(guó)人中上升到100%，在非洲裔美國(guó)人中上升到75%。攜帶有這兩種基因突變的人一生中罹患腸癌的風(fēng)險(xiǎn)幾乎是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.

對(duì)于BRCA基因，94%的非德系猶太人和19%的德系猶太人攜帶有可能被遺漏的基因突變。同樣，亞裔(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.”

他補(bǔ)充說(shuō)：“臨床假陰性的結(jié)果可能是誤導(dǎo)性的安慰，使人們不再接受需要基于風(fēng)險(xiǎn)而進(jìn)行的預(yù)防性治療。人們可能會(huì)患上原本可以預(yù)防的癌癥。”

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.”

針對(duì)這些發(fā)現(xiàn)，23andMe在一份聲明中表示：“競(jìng)爭(zhēng)對(duì)手聲稱我們正將‘臨床假陰性結(jié)果’退回是假消息，其對(duì)本公司測(cè)試的特征描述也是錯(cuò)誤的。我們的測(cè)試非常準(zhǔn)確。作為FDA授權(quán)檢測(cè)過(guò)程的一部分，我們已經(jīng)證明，我們的健康產(chǎn)品基因變異測(cè)試準(zhǔn)確性超過(guò)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.”

該公司表示，已向客戶明確表示，只檢測(cè)某些基因變異，客戶不應(yīng)放棄任何基于23andMe結(jié)果的推薦檢測(cè)。該公司表示：“這不是診斷測(cè)試。如果一個(gè)人有癌癥家族史或其他臨床檢測(cè)的適應(yīng)癥，我們一直建議首先咨詢醫(yī)療機(jī)構(gòu)。”

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”.

南安普頓大學(xué)臨床遺傳學(xué)家安妮克•盧卡森教授表示，根據(jù)她的經(jīng)驗(yàn)，非專業(yè)人士很可能會(huì)錯(cuò)誤地將陰性結(jié)果解讀為“沒(méi)有風(fēng)險(xiǎn)”。

“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.”

她說(shuō)：“我確實(shí)認(rèn)為假陰性率是個(gè)問(wèn)題，這不一定是由于公司的失誤，而是由于人們的普遍意識(shí)不強(qiáng)。大多數(shù)來(lái)診所的人會(huì)問(wèn)：‘我有乳腺癌的基因嗎?’想象一下，這是一個(gè)單一的測(cè)試，而不是通過(guò)檢查大約兩萬(wàn)個(gè)基因序列編碼來(lái)判斷哪些有所不同。”