Rare Genetic Mutation Linked to 62-Fold Higher Lung Cancer Risk in Nonsmokers

A rare genetic mutation that raises lung cancer risk 62-fold in nonsmokers has been identified.

According to U.S. biotech news outlet Fierce Biotech, the findings were published on the 17th in the journal Science.

Researchers analyzed genetic data from 3.37 million people in the 23andMe database to identify the T790M mutation in the epidermal growth factor receptor (EGFR). They found the mutation in about 1 in 15,850 people.

Among the 17 cancers and nonlung diseases examined, the mutation showed a strong association only with lung cancer. Smoking itself raised the risk of lung cancer in the general population by just fourfold.

The researchers traced the mutation’s origins to populations in the Appalachian region of the southern United States.

Corresponding author Pasi Jänne, a lung cancer specialist at Dana-Farber Cancer Institute, told Fierce Biotech, “Current lung cancer screening is based almost entirely on tobacco exposure,” adding, “People with genetic risk factors could benefit from early screening and detection.”

EGFR is a protein that regulates cell growth and division. Mutations can enable cancer cells to grow and spread. EGFR mutation-positive lung cancer accounts for about 10-15% of lung cancer cases in the United States and is more common among Asians.

Smoking is a leading cause of lung cancer, but patients whose cancer is caused by EGFR mutations are generally nonsmokers.

Jänne cautioned, however, that the study does not fully show lifetime risk, adding, “There may be other genetic and environmental factors that modify risk.”

Treatments for EGFR-mutated lung cancer include Tagrisso from AstraZeneca and Rybrevant from Johnson & Johnson. AstraZeneca announced in 2015 that the median progression-free survival was 13.5 months in patients with the T790M mutation; the data later led to U.S. Food and Drug Administration (FDA) approval.

Some treatments, however, encountered development setbacks. In 2015, Germany’s Boehringer Ingelheim agreed to pay South Korea’s Hanmi Pharmaceutical up to $730 million for the rights to the oral tyrosine kinase inhibitor olmutinib, but withdrew from the deal a year later after the drug caused a life-threatening skin disorder. Hanmi Pharmaceutical ultimately discontinued olmutinib’s development.