這種罕見基因會顯著增加從未吸煙者罹患肺癌的風險（1/2）

Recently The New York Times reported the following:

This Rare Gene Drastically Raises Lung Cancer Risk in People Who Never Smoked (1/2)

The gene is found predominantly in Southern Appalachia and may be one of the most powerful cancer-risk mutations ever found.

The NYT - By Gina Kolata (Gina Kolata reports on diseases and treatments, how treatments are discovered and tested, and how they affect people.)

Sept. 17, 2026

Between 200 and 225 years ago, someone or several someones from the British Isles had a gene mutation that caused lung cancer. They traveled to America, settled in Southern Appalachia and transmitted the cancer gene to their descendants and their descendants’ descendants.

Today that lung cancer gene, known as EGFR T790M, is found largely in residents of the United States and mostly in Southern Appalachia, especially Tennessee and Alabama. It makes lung cancer 62 times as likely in those who have never smoked and 10 times as likely in smokers.

Those are among the stunning findings of a new report, published on Thursday in Science by researchers at the Dana-Farber Cancer Institute and 23andMe Research Institute.

The gene is one of the most powerful, if not the most powerful, cancer-risk mutations ever found, said Alexander Gusev, a geneticist at Dana-Farber and an author of the paper.

Unlike other cancer genes that can cause cancer in a variety of organs, this gene is associated only with lung cancer. Researchers expect their discovery can help unlock secrets about the development of the disease.

For those with the gene, the hope is for early detection and treatment or even cancer prevention, said Dr. Raymond DuBois, the director of the Medical University of South Carolina’s Hollings Cancer Center, who was not associated with the work.

“This is a great story,” Dr. DuBois said, adding that he “read the paper like a novel.”

The variant was discovered in 2005, but because it is so rare, researchers were limited to studying families in which several members had the gene and got lung cancer. Studies like that could not reveal how much the gene increased risk.

Investigators did learn, though, that the variant was unusual. Lung cancer patients often have mutations in the EGFR gene, but those mutations arose by random bad luck later in life. If those mutations arise in embryos, they kill the embryos. But not the EGFR T790M mutation. People are born with it, and it is not lethal. It causes only lung cancer, but decades later.

Dr. Jaclyn LoPiccolo and Dr. Pasi A. Jänne, lung cancer experts at Dana-Farber, realized that 23andMe’s data might hold the key to figuring out how dangerous EGFR T790M is. Other databases had too few people — less than a million participants, only a handful of whom had the mutation. But 23andMe, a direct-to-consumer recreational databank that many use to find ancestors, was huge.

The database had more than 10 million people who had consented to participate in research, including the 3.37 million who had provided both genetic data and information on whether they had lung cancer. There were 641 who had the mutation.

(to be continued)

Translation

這種罕見基因會顯著增加從未吸煙者罹患肺癌的風險（1/2）

該基因主要發現於美國 Appalachia 南部地區，可能是迄今為止的最強致癌基因突變之一

大約在 200 到 225 年前，來自不列顛群島的人一個或幾個的人是帶有一種導致肺癌的基因突變。他們遷移到美國，定居在 Appalachia 南部地區，並將這種致癌基因遺傳給了他們的後代以及其後代的後代。

如今，這種被稱為 EGFR T790M 的肺癌基因很大程度上存在於美國居民中，主要是在Appalachia 南部地區，尤其是田納西州和阿拉巴馬州。這種基因使從未吸煙者罹患肺癌的風險增加62倍，吸煙者罹患肺癌的風險增加10倍。

這些令人震驚的發現來自 Dana-Farber 癌症研究所和 23andMe 研究機構的研究人員於週四在《科學》雜誌上發表的一份新報告。

Dana-Farber 癌症研究所的遺傳學家、論文的作者之一 Alexander Gusev 表示，這種基因是迄今為止發現的最強大的癌症風險突變之一，甚至可能就是最強大的。

與其他可導致多種器官癌症的基因不同，這種基因僅與肺癌有關。研究人員希望他們的發現能幫助揭開肺癌發展的奧秘。

並未參與這項研究的南卡羅來納醫科大學 Hollings 癌症中心主任 Raymond DuBois 博士表示，對於攜帶這種基因的人來說，希望在於能夠早期發現並治療，甚至預防癌症。

DuBois 博士說：「這是一個很棒的故事」。他還補充說，他「像看小說一樣讀完了這篇報告」。

這種變異於2005年被發現，但由於其極為罕見，研究人員只能研究那些有多位成員帶有該基因並患有肺癌的家族。此類研究無法揭示該基因究竟增加了多少患病風險。

不過，研究人員確實發現這種變異很特殊。肺癌患者的 EGFR 基因通常有突變，但這些突變往往是晚年因隨機的厄運而偶然發生的。如果這些突變發生在胚胎時期，則會導致胚胎死亡。但EGFR T790M 突變並非如此。人們出生時就帶有這種突變，而且它並非致命。它只會導致肺癌，但通常是在數十年後。

Dana-Farber 癌症研究所的肺癌專家 Jaclyn LoPiccolo 博士和 Pasi A. Jänne 博士意識到，23andMe的數據或許能揭示 EGFR T790M 的危險程度。其他資料庫的人數太少 - 參與者不到百萬，其中只有極少數人帶有這種突變。但  23andMe 是一家面向消費者的休閒基因資料庫，許多人利用它來尋找祖先，規模非常龐大。

該資料庫擁有超過 1,000 萬名同意參與研究的人，其中包括 337 萬名同時提供了基因數據和是否患肺癌病的資訊。其中有 641 人帶有該突變。

（待續）