Science (New York, N.Y.) · 2026
Germline EGFR T790M mutation and lung cancer risk.
СтатьяНазвание и аннотация: Перевод в очереди
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LoPiccolo Jaclyn, Micheletti Steven, Shi Jing, Wang Wei, Saini Shubham, Lin Keng-Han, Xu Wanwan, Fontanillas Pierre, 23andMe Research Team3‡, Koeller Diane R, Yatzus Helen, Williamson Victoria G, Avila Jose A, Liautaud Raphael B, Fields Noah D, Harper Allison, Kotait Virginia, Izzo Ericka, Ciupek Andrew, Granville Courtney A, Collins Ryan L, Garber Judy E, Christiani David C, Aslibekyan Stella, Granka Julie M, Gusev Alexander, Jänne Pasi A
Аннотация
Most lung cancers are tobacco related, with genetic factors influencing smoking behavior identified through genome-wide association studies. However, inherited risk in familial and non-smoking-related lung cancers, including risk in carriers of EGFR T790M, remains poorly understood. Here, in more than 3.3 million individuals, the EGFR T790M germline variant is significantly associated with lung cancer risk, with no increased risk for 17 other cancers and no interaction with polygenic risk. This risk exceeds that conferred by smoking and is several-fold higher in never-smokers. Global geographic and ancestry analyses show higher T790M prevalence in the US than in British- and Irish-descendant populations, reflecting a Southern Appalachian founder event about 200 to 225 years ago, increasing regional prevalence and affecting those of British, Irish, and African descent. Recognition of high-risk carriers may inform targeted genetic testing and screening strategies.