Rare Inherited Gene Mutation Linked to Sharp Rise in Lung Cancer Risk

A rare inherited mutation in the Epidermal Growth Factor Receptor (EGFR) gene is associated with a substantially higher risk of lung cancer, according to a study drawing on genetic data from more than 3.3 million people in the 23andMe database.

The variant, known as EGFR T790M, was linked to an overall 25-fold increase in lung cancer risk. Among smokers who carried it, the odds of developing the disease were 10 times higher. Among never-smokers, carriers were more than 60 times as likely to develop lung cancer as those without the mutation, the researchers reported in the journal Science.

The mutation did not show an association with any of 17 other common cancers examined, suggesting its effects may be largely confined to lung cancer.

Up to 20% of lung cancer patients have never smoked. The findings, the researchers said, could help doctors identify high-risk individuals in advance and monitor them more intensively.

"Today, lung cancer screening is driven almost entirely by smoking history," study leader Dr. Jaclyn LoPiccolo of the Dana-Farber Cancer Institute in Boston said in a statement. "Our findings raise the possibility that, in the future, screening could also be dictated by inherited genetic risk."

EGFR T790M was first identified in 2005 in a European family with multiple cases of lung cancer, and has since been found in other families with unusually high rates of the disease.

"For years we've known that some families inherit a markedly increased risk of lung cancer, but because this variant is so rare, we've never been able to accurately measure that risk," said study co-author Dr. Pasi A. Jänne, also at Dana-Farber. "By studying more than three million people, we were able to demonstrate just how strongly this inherited mutation is associated with lung cancer."

In a separate study, researchers found that a simple intervention using a local anesthetic can make the insertion of an intra-uterine device (IUD) significantly less painful. The procedure has traditionally been performed without any pain relief.

In a trial of 370 women who had never given birth, half received a small amount of the local anesthetic mepivacaine delivered into the uterus through a thin plastic catheter minutes before the procedure, while the others received saline as a control.

On a scale of 0 to 100, the average pain score during the procedure was 43.8 with mepivacaine compared with 58.6 with placebo. The proportion of participants who found the pain tolerable rose from 91.4% with saline to 98.3% with the anesthetic, according to the report published in JAMA.

"Considering the frequency of IUD placements worldwide, even modest reductions in the proportion of individuals experiencing intolerable pain may have important clinical implications," the researchers wrote.

Co-author Dr. Helena Kopp Kallner of the Karolinska Institutet in Sweden said the method works when compared with no active treatment, but added that it also needs to be compared with other pain relief methods.