U.S. — Dr. Jaclyn LoPiccolo, an attending physician and lung-cancer researcher at Dana Farber Cancer Institute, co-led the research team for the study. The researchers used genetic data from the company 23andMe for the study to analyze the specific EGFR mutation called T790M. "While we knew that T790M was associated with lung cancer, we didn’t have a population large enough to determine how common the variant was, how strong its effect, and how the risk varies in different groups," LoPiccolo said.

She added that the rarity of the variant required a massive dataset to yield reliable statistics. "This mutation is so rare that we weren’t able to get population-level risk estimates without the size of a database like that from 23andMe," she said.

Among nonsmokers, carriers of the EGFR T790M mutation have a 25-fold increased risk of developing lung cancer compared to non-carriers. The T790M mutation was first discovered in a European family in 2005. Members of the European family where the T790M mutation was discovered had not smoked but developed lung cancer. Approximately one in 15,000 people in the U.S. carry the T790M mutation.

The rate of the T790M mutation is approximately one in 2,000 in Southern Appalachia. Between 10% and 20% of lung cancer cases in the U.S. each year are diagnosed in people who never smoked.

Current lung cancer screening guidelines recommend low-dose radiation CT scans only for people with a heavy smoking history above a certain age. There are currently no evidence-based recommendations for monitoring lungs for signs of cancer in carriers of the T790M mutation. Dr. Jaclyn LoPiccolo is conducting a study called INHERIT.

The INHERIT study includes people from across the country with any inherited genetic risk for lung cancer, including the EGFR T790M mutation. "The goal is to use CT screening to detect lung cancer at the earliest, most curable stage when it can be removed or cured," LoPiccolo said.

The Susan Wojcicki Foundation funded the study. Nadia Litterman is the executive director of the Wojcicki Foundation. Wojcicki was the former CEO of YouTube.

Wojcicki died of lung cancer in 2024. Wojcicki never smoked. "I do think that understanding your risk of lung cancer, especially from a genetic perspective, along with your exposures to things like radon and other environmental factors, would be really valuable," Litterman said. She noted that existing protocols lag behind the scientific understanding of genetic risks. "The lung-cancer guidelines are not quite there yet, but it’s a pretty clear path of what it could look like for people who are carriers of this mutation," she said. "They could be screened on a more regular basis, and if they develop cancer, and it’s caught early, they would have a much better trajectory than if they didn’t know about [their genetic] risk." "That’s the world we are trying to work toward, and this is a major step toward that," she said.

Frank McKenna is a personal trainer in Virginia Beach. Frank McKenna is 66 years old. Frank McKenna never smoked.

Frank McKenna was diagnosed with Stage IV lung cancer in 2016. Genetic testing of fluid drained from Frank McKenna's lung identified the EGFR T790M mutation. A biopsy from Frank McKenna's lung lesion confirmed the T790M mutation. Frank McKenna started targeted therapy designed to neutralize the T790M mutation. "When I started that targeted therapy, which is a pill I take once a day, within a couple of days, I could feel a difference," McKenna said. He described the severity of his condition before treatment began. "I had lost weight, and there was cancer in various parts of my body, including in my bones, where it had spread," he said. "But I could feel my life coming back." Frank McKenna continues to take targeted therapy today. Frank McKenna receives CT scans every six to seven months.

Frank McKenna's daughter is 33 years old. Frank McKenna's daughter was diagnosed with melanoma in her ear a few months after his diagnosis. Frank McKenna's daughter carries the T790M mutation.

McKenna expressed hope that early detection could alter the course of the disease for his daughter. "If something were to appear, she can catch it at an early stage, perhaps Stage I, and not go through Stage IV, because there are not as many options, and the outlook is not as positive," McKenna said.

Why It Matters

The study establishes a quantifiable link between a rare inherited mutation and lung cancer risk in nonsmokers, a group that accounts for 10% to 20% of U.S. cases annually. By leveraging data from 23andMe, researchers overcame the statistical limitations posed by the mutation's rarity, which affects approximately one in 15,000 Americans overall and one in 2,000 in Southern Appalachia. This finding challenges current screening guidelines that restrict low-dose CT scans to heavy smokers, leaving carriers of the T790M mutation without evidence-based monitoring protocols.

The research builds on the initial discovery of the T790M mutation in a nonsmoking European family in 2005 and shows the potential for genetic screening to identify high-risk individuals before symptoms arise. With targeted therapies available for those who test positive, as demonstrated by Frank McKenna’s experience since 2016, early detection could improve outcomes. The ongoing INHERIT study aims to define these screening protocols, while advocates like the Wojcicki Foundation push for guidelines that reflect genetic risk alongside environmental factors.

Timeline

Wojcicki died of lung cancer in 2024. A study published in Science reports that an inherited genetic mutation in the EGFR gene is associated with a 25-fold higher risk of developing lung cancer compared to people without the mutation, regardless of smoking status.

What's New

Later reporting identifies Jaclyn LoPiccolo as a researcher. Additional context confirms that EGFR T is a genetic variant.