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Rare Inherited EGFR T790M Variant Greatly Raises Lung Cancer Risk

The new population-scale analysis could push trials of targeted low-dose CT screening after it found especially large cancer odds for people who never smoked.

Overview

  • A Science study published Sept. 17, 2026 analyzed genetic and health data from more than 3.3 million 23andMe users and identified 641 carriers of the inherited EGFR T790M variant.
  • Carriers faced about a 25-fold higher overall odds of lung cancer and roughly a 60-fold higher risk among people who never smoked, according to the study’s population estimates.
  • The variant is rare overall—about 1 in 15,850 people—but is much more common in parts of Southern Appalachia, where researchers traced a likely founder introduction from the British Isles.
  • Clinical work is already under way: Dr. Jaclyn LoPiccolo’s INHERIT prospective study and a trial testing low-dose CT screening in carriers aim to define when and how often mutation carriers should be screened, though guidelines have not changed.
  • Key unknowns remain because the cohort was mainly of European ancestry and the variant is rare, so researchers are studying age-related risk, environmental interactions such as radon or air pollution, and how carrier detection should shape treatment and equity in care.