Rare genetic variant EGFR T790M is highly associated with lung cancer risk in never-smokers

2026/09/26 11:45

Medical institutions conduct low-dose computed tomography (LDCT) lung cancer screening. The latest research found that the rare congenital EGFR T790M mutation is highly associated with the risk of lung cancer in non-smokers. (File photo)

[Compiled by Chen Chengliang/Comprehensive Report] Many lung cancer patients have never smoked in their lives, and it is often difficult to explain the cause of the disease clinically. A large genetic study analyzing more than 3.3 million people found that some non-smokers' cancer risk may be due to innate inheritance; among never-smokers, those with specific rare genetic mutations have a relative risk of developing lung cancer that is more than 60 times higher than those without the cause.

The US "Time" magazine (TIME) reported that this study, conducted by the Dana-Farber Cancer Institute affiliated with Harvard Medical School and the personal genetic testing company 23andMe, has been published in the journal Science. Researchers analyzed the de-identified genetic data of more than 3.3 million participants and found that regardless of whether they smoked or not, the overall risk of lung cancer for those with the mutation was about 25 times that of those without the mutation.

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This mutation is "T790M" in the epidermal growth factor receptor (EGFR) gene. It is a germline mutation inherited from parents and present in cells throughout the body, rather than an acquired mutation that appears in tumors after lung cancer occurs. Among those who have never smoked, the risk of carriers is more than 60 times higher; however, the research team emphasizes that this is a relative risk comparison between the two groups, and it does not mean that the chance of cancer among non-smokers increases by 60 times out of thin air.

Can rare mutations be included in lung cancer screening in the future?

The study points out that this mutation is quite rare, with only about 1 in 15,000 people in the United States carrying it. In addition, the study did not find the same risk association between T790M and 17 other common cancers.

This discovery has led the medical community to explore the feasibility of incorporating genetic information into early screening. Currently, lung cancer screening in various countries is mainly based on smoking history and other conditions. The Dana-Farber research team is promoting follow-up research to evaluate whether personalized low-dose computed tomography (LDCT) tracking can be arranged for non-smokers with genetic risks in the future.

However, the research team emphasized that the current results only confirm the strong association between this genetic variation and lung cancer. It does not yet mean that all non-smokers need to be tested, and the current screening guidelines have not changed. Whether screening strategies can be adjusted based on genetic risk in the future still requires further research to confirm.

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