Individuals who have never engaged in smoking might still face a high risk of developing lung cancer due to a rare genetic mutation. A recent study indicates that carriers of the EGFR T790M mutation may have a 62-fold increased risk of lung cancer compared to those who have never smoked.

Even when considering both smokers and non-smokers, those with the mutation encounter approximately 25 times the risk of developing lung cancer. Dr. Jaclyn LoPiccolo, an expert involved in the study, expressed: “Lung cancer risks are often attributed to smoking and environmental exposures, yet in certain individuals, inherited genetics can significantly influence risk.”

She further elaborated that while inherited risk for common diseases is typically dispersed across numerous genetic variants with minor impacts, this particular mutation is associated with a substantial increase in lung cancer risk.

Lung cancer remains one of the most prevalent cancers affecting both men and women in the United States. The American Cancer Society anticipates around 229,410 new cases by 2026. It is also the leading cause of cancer-related deaths in the nation, accounting for one out of five cancer fatalities.

Tobacco smoking is the primary lung cancer risk factor, contributing to about 80 percent of related deaths. Other risk elements include air pollution and genetic predisposition, which are beyond lifestyle control.

Although inherited genetic factors and family history are acknowledged to elevate lung cancer risks, their understanding remains incomplete. The study, published in Science, examines the EGFR T790M mutation using genetic and health data from over 3 million individuals.

The findings reveal a strong connection between this gene variant and lung cancer risk. Researchers traced the mutation’s history, noting its arrival in the United States roughly 200 years ago, with origins linked to the Southern Appalachian region.

LoPiccolo said the study showed that carriers of the inherited EGFR T790M mutation have 25 times higher odds of developing lung cancer compared to non-carriers, with particularly striking odds in non-smokers.

The researchers aim to leverage this information to identify patients who might benefit from genetic testing and lung cancer screening.

Despite the mutation’s rarity, the study had access to over 3.3 million genotyped samples, allowing for detailed analysis of its cancer risk association. Around 1 in 15,850 participants carried the mutation, and it was significantly prevalent in the United States.

The mutation’s carrier frequency was notably high among those with British and Irish ancestry, as well as those of African and Indigenous American origins.

This suggests a European origin for the mutation, brought to the Southern Appalachian region by British and Irish settlers during colonial times.

LoPiccolo acknowledged the need for further research on the mutation’s implications for carriers. “We aim to understand how lung cancer risk evolves with age for mutation carriers, their lifetime risk, and the factors influencing why some carriers develop lung cancer while others do not,” she said.

She concluded that the ultimate objective is to employ this data to guide CT screening, effectively identifying at-risk individuals.