Rare inherited EGFR mutation linked to 25-fold increased lung cancer risk in nonsmokers

A landmark study published in Science reveals that the rare inherited EGFR T790M genetic mutation increases lung cancer risk by 25-fold overall, and by over 60-fold in nonsmokers. Analyzing data from 3.3 million 23andMe participants, researchers from Dana-Farber Cancer Institute traced the mutation's lineage to British and Irish settlers in Southern Appalachia, where prevalence rises to 1 in 2,000. The findings challenge current screening guidelines, which rely almost entirely on smoking history.

EGFR T790M mutation

• ▪The EGFR T790M mutation was first identified in 2005 within a European family that exhibited unusually high rates of lung cancer.
• ▪The EGFR T790M mutation was not linked to any of the 17 other common cancers analyzed in the study published in Science.
• ▪The rare inherited EGFR T790M genetic mutation is associated with a 25-fold increased risk of developing lung cancer compared to noncarriers.

Nonsmoker cancer cases

• ▪The proportion of lung cancer cases diagnosed in people who have never smoked has been rising, though the underlying genetic factors remain poorly understood.
• ▪Nonsmokers account for approximately 10% to 20% of all lung cancer cases diagnosed annually in the United States.

23andMe genetic study

• ▪The study on the EGFR T790M mutation was co-led by Dr. Jaclyn LoPiccolo and co-senior authors Dr. Pasi A. Jänne and Dr. Alexander Gusev of the Dana-Farber Cancer Institute.
• ▪Investigators at the Dana-Farber Cancer Institute and the 23andMe Research Institute analyzed de-identified, aggregated genetic data from 3.3 million research-consented participants.

Future screening strategies

• ▪Current clinical guidelines in the United States restrict lung cancer screening recommendations almost entirely to individuals with a heavy smoking history.
• ▪The INHERIT Study, led by Dr. Jaclyn LoPiccolo and Dr. Pasi A. Jänne, is actively recruiting participants to further investigate inherited genetic risks for lung cancer.

Southern Appalachia prevalence

• ▪In Southern Appalachia, the prevalence of the EGFR T790M mutation rises to approximately 1 in 2,000 people.
• ▪Researchers traced the ancestral lineage of the EGFR T790M mutation to British and Irish settlers who arrived in the United States about 200 years ago.
• ▪The prevalence of the EGFR T790M mutation is approximately 1 in 15,000 people across the general United States population.