一种罕见的基因突变可能使人们即使从未吸烟，患肺癌的风险也大幅升高。
A rare genetic mutation could put people at a dramatically higher risk of developing lung cancer even if they’ve never smoked.
《科学》杂志发表的一项新研究发现，EGFR基因中的T790M突变可使携带者的肺癌风险较没有该突变者升高至25倍。
A rare mutation in the gene EGFR T790M was found to increase lung cancer risk by 25 times compared with people who did not have the mutation, according to a new study published in the journal Science.
在从未吸烟的人群中，携带该突变者患肺癌的几率约为没有该突变的从不吸烟者的62倍。
A rare mutation in the gene EGFR T790M was found to increase lung cancer risk by 25 times compared with people who did not have the mutation, according to a new study published in the journal Science.
胰腺癌疫苗首次人体试验显现希望，可预防高风险患者发病。该研究由达纳-法伯癌症研究所和23andMe研究所的研究人员牵头，分析了330多万人的人口数据。该基因变异在研究所涵盖的其他17种癌症中均未显示风险升高。
Among people who had never smoked, carriers of the mutation had about 62 times the odds of lung cancer compared with never-smokers who did not have it. PANCREATIC CANCER VACCINE SHOWS PROMISE IN FIRST HUMAN TRIAL, PREVENTING DISEASE IN HIGH-RISK PATIENTS The study, led by investigators at Dana-Farber Cancer Institute and 23andMe Research Institute, analyzed data from more than 3.3 million people.
达纳-法伯癌症研究所主治医师、肺癌研究员雅克琳·洛皮科洛在新闻稿中表示：“目前，肺癌筛查几乎完全以吸烟史为依据。”
The gene variant showed no increased risk across 17 other cancers studied.
癌症警示信号可能在血液检测发现异常数年前就出现在DNA中。“我们的研究结果提出了一种可能性：未来的筛查也可能以遗传风险为依据。如果进一步研究证实这种做法有益，人们可以通过基因检测识别出携带EGFR T790M突变的人，并为她们提供个性化CT筛查，以便在肺癌最容易治愈的阶段将其发现。”研究人员发现，美国大多数该突变携带者具有共同的祖源，可追溯至约200至225年前定居在美国南部阿巴拉契亚地区的英国和爱尔兰移民。
"Today, lung cancer screening is driven almost entirely by smoking history," study co-author Jaclyn LoPiccolo, attending physician and lung cancer researcher at Dana-Farber Cancer Institute, said in a press release. CANCER WARNING SIGNS MAY APPEAR IN DNA YEARS BEFORE BLOOD TESTS DETECT TROUBLE "Our findings raise the possibility that, in the future, screening could also be dictated by inherited genetic risk. If further studies confirm the benefit, people with EGFR T790M could be identified through genetic testing and offered personalized CT screening to identify lung cancers when they are at their most curable stage." Most U.S. carriers of the mutation were traced to a shared ancestry linked to British and Irish settlers in Southern Appalachia about 200–225 years ago, the researchers found.
这种突变在全美仍较为罕见，约每1.5万至1.6万人中就有1人携带。在美国南部阿巴拉契亚地区的一些地方，这种突变更为常见，研究人员估计每2000人中可能有多达1人携带。
CANCER WARNING SIGNS MAY APPEAR IN DNA YEARS BEFORE BLOOD TESTS DETECT TROUBLE "Our findings raise the possibility that, in the future, screening could also be dictated by inherited genetic risk. If further studies confirm the benefit, people with EGFR T790M could be identified through genetic testing and offered personalized CT screening to identify lung cancers when they are at their most curable stage." Most U.S. carriers of the mutation were traced to a shared ancestry linked to British and Irish settlers in Southern Appalachia about 200–225 years ago, the researchers found.
点击此处查看更多健康相关资讯：“我们发现，绝大多数携带这种突变的人都是从同一个祖先谱系中继承下来的，”LoPiccolo说道。“我们可以将这个祖先谱系追溯到那些移民到美国的英国和爱尔兰人，并证明：大约200年前，在美国南部阿巴拉契亚地区发生了一次‘奠基者事件’（即少数人主导了人口繁衍的过程）以及一次‘基因瓶颈’（即基因多样性急剧下降的现象）之后，这种突变在人群中的比例开始显著增加。”
The mutation remains rare nationwide, affecting roughly one in 15,000–16,000 people. It is more common in some parts of Southern Appalachia, where researchers estimate as many as one in 2,000 people may carry it. CLICK HERE FOR MORE HEALTH STORIES "We found that the vast majority of carriers inherited the mutation from the same ancestral lineage," said LoPiccolo. "We could trace that lineage to British and Irish settlers in the United States and show that the mutation became enriched after a founder event and genetic bottleneck in Southern Appalachia about 200 years ago.
“这是一个非常有趣的例子，它展示了人类迁移和家族谱系如何影响后代的疾病风险，”Dana-Farber研究所的定量遗传学家Alexander Gusev指出。“这项研究的一个‘显著’发现是：一个单一的基因突变竟然能够对疾病风险产生如此巨大的影响。”
"It's a fascinating example of how human migration and genealogy can shape disease risk, generations later." One of the "remarkable" findings of the study was the fact that a single mutation could have such a strong effect, according to Alexander Gusev, a quantitative geneticist at Dana-Farber.
Gusev在新闻稿中表示：“据我所知，这可能是迄今为止发现的、与癌症风险增加最相关的突变之一——甚至可能是最强的突变。”他补充道：“吸烟对肺癌有害，而这种突变同样对肺癌有负面影响；如果两者同时存在，你的患病风险将是两者风险的总和。因此，绝对不要吸烟。”
"To my knowledge, it's one of the strongest, if not the strongest, cancer risk-increasing mutations that has ever been found," he said in the release. CLICK HERE TO "Smoking is bad for lung cancer. This mutation is bad for lung cancer. When you do both, your risk is the sum of those two risks," he added. "So, you definitely don't want to smoke." The researchers suggest that people with a strong family history of lung cancer, multiple lung nodules or tumors or family roots in parts of the southeastern U.S. should consider speaking with a genetic counselor about whether genetic testing or lung cancer screening makes sense for them.
研究人员建议：那些有肺癌家族史、肺部有多个结节或肿瘤的人，或者家族祖籍在美国东南部地区的人，应该考虑咨询遗传咨询师，以确定是否需要进行基因检测或肺癌筛查。
CLICK HERE TO "Smoking is bad for lung cancer. This mutation is bad for lung cancer. When you do both, your risk is the sum of those two risks," he added. "So, you definitely don't want to smoke." The researchers suggest that people with a strong family history of lung cancer, multiple lung nodules or tumors or family roots in parts of the southeastern U.S. should consider speaking with a genetic counselor about whether genetic testing or lung cancer screening makes sense for them.
不过，这项研究也存在一些局限性：由于这种突变极为罕见，即使在数百万参与者中，研究人员也只检测到了少数携带者；因此，这种突变究竟会带来多大的健康风险仍不确定。
There were some limitations to the study. Because the mutation is so rare, researchers identified relatively few carriers even among the millions of participants, meaning the exact size of the increased risk remains uncertain.
此外，这项分析在很大程度上依赖于23andMe公司的研究数据，但这些数据可能无法代表更广泛的人群。另外，由于这种突变在美国某些地区的发病率较高，因此研究得出的风险估计结果可能并不适用于所有人。
TEST YOURSELF WITH OUR LATEST LIFESTYLE QUIZ The analysis also relied heavily on 23andMe research participants, who may not represent the broader population. Because the mutation is much more common in certain parts of the U.S., the risk estimates may not apply equally to everyone, the researchers noted.
尽管该研究证实了基因检测与肺癌风险之间存在很强的关联，但并未证明基因检测能够降低死亡率或改善其他健康结局。该研究部分由美国国立卫生研究院和美国癌症协会资助。
While the study establishes a strong association with lung cancer risk, it does not demonstrate that genetic testing improves mortality or other health outcomes. The study was funded in part by the National Institutes of Health and the American Cancer Society.