A recent study published in Science has identified a rare genetic mutation that dramatically increases the risk of lung cancer, even for people who have never smoked. Researchers at the Dana‑Farber Cancer Institute and the 23andMe Research Institute analyzed data from more than 3.3 million participants and found that carriers of the EGFR T790M mutation are about 25 times more likely to develop lung cancer than non‑carriers.

Higher Risk for Never‑Smokers

Among individuals who have never smoked, the mutation’s impact is even more striking. Never‑smokers with EGFR T790M have roughly 62 times the odds of developing lung cancer compared with never‑smokers who lack the mutation. The researchers emphasized that the gene did not increase risk for any of the 17 other cancers examined.

Geographic Concentration in Southern Appalachia

The study traced most U.S. carriers of the mutation to a shared ancestry linked to British and Irish settlers who arrived in Southern Appalachia about 200–225 years ago. While the mutation is rare nationwide—affecting roughly one in 15,000–16,000 people—it is considerably more common in that region, with an estimated prevalence of one in 2,000 residents.

Implications for Screening

Current lung‑cancer screening guidelines rely almost entirely on smoking history, according to study co‑author Dr. Jaclyn LoPiccolo, an attending physician at Dana‑Farber. The researchers suggest that, if future studies confirm the benefit, genetic testing could identify individuals with EGFR T790M and direct them to personalized CT screening programs, catching cancers at a stage when they are most treatable.

Expert Commentary

Dr. Alexander Gusev, a quantitative geneticist at Dana‑Farber, called the finding “one of the strongest, if not the strongest, cancer‑risk‑increasing mutations ever discovered.” He added, “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. So, you definitely don’t want to smoke.”

Who Should Consider Testing?

The authors recommend that people with a strong family history of lung cancer, multiple lung nodules or tumors, or ancestry rooted in the southeastern United States discuss genetic counseling with their physicians to determine whether testing or earlier screening might be appropriate.

Study Limitations

Because the mutation is so rare, the study identified relatively few carriers among the millions of participants, leaving some uncertainty about the precise magnitude of risk. Additionally, the analysis relied heavily on 23andMe research participants, who may not fully represent the broader U.S. population. The researchers caution that while the association between EGFR T790M and lung cancer is strong, further work is needed to prove that genetic testing will improve mortality or other health outcomes.

Funding

The research was funded in part by the National Institutes of Health and the American Cancer Society.

Original reporting: Fox News (HLL/CB) — read the source article.