Health and Me

Rachel V Thomas

Never Smoked, Still Got Lung Cancer? Rare Gene Mutation Linked To Over 60x Risk

<span><a href="https://www.healthandme.com/health/lung-cancer">Lung cancer</a></span> in people who have never smoked is an increasingly recognized global health concern. A new study found that a rare inherited <span>EGFR</span> mutation may increase <span>lung</span> cancer risk by over 60 times in never-smokers.

Lung cancer in never-smokers is the seventh leading cause of cancer death worldwide. Approximately 60% to 80% of lung cancer cases in never-smokers globally occur in females.

The study, published in <em>Science</em>, found that a rare inherited EGFR T790M mutation can increase lung cancer risk by over 60 times in never-smokers and 25 times in smokers.

<span>Smoking</span> itself increases the risk of developing lung cancer fourfold in the general population.

To look for the rare mutation, researchers evaluated genotyping data from 3.37 million people and found that it occurs in about 1 in 15,850 people.

Among the 17 cancers and non-pulmonary conditions screened, the mutation showed a strong association only with lung cancer. Researchers also traced its origin to southern Appalachian populations in the US.

“Recognition of individuals more likely to carry <em>EGFR</em> T790M, including those with family history of lung cancer, multifocal lung cancer, or lung nodules or Southeastern US ancestry, may help to inform future screening and prevention strategies for those at highest risk,” said the researchers.

“Smoking is bad for lung cancer. This mutation is bad for lung cancer. When you do both, your risk is the sum of those two risks,” said Alexander Gusev, a quantitative geneticist at Dana-Farber. “So, you definitely don't want to smoke.”

The mutation was not linked to any of the 17 other common cancers studied, suggesting that its effects may be largely limited to lung cancer.

<h2>Could Genetic Testing Change Lung Cancer Screening?</h2>

“Today, lung cancer screening is driven almost entirely by smoking history,” said Jaclyn LoPiccolo, attending physician and lung cancer researcher at Dana-Farber Cancer Institute, who co-led the study.

LoPiccolo added that the findings raise the possibility that, in the future, screening could also be dictated by inherited genetic risk.

“If further studies confirm the benefit, people with EGFR T790M could be identified through genetic testing and offered personalized CT screening to identify lung cancers when they are at their most curable stage,” she said.

<h2>How Does The Mutation Increase Risk?</h2>

Although most lung cancers are associated with tobacco use or exposure, the proportion diagnosed in people who have never smoked has been rising. Yet the genetic factors underlying these cancers, particularly the role of inherited risk, are not well understood.

In 2005, researchers identified the rare inherited EGFR T790M mutation in a European family with multiple cases of lung cancer. Since then, the mutation has been reported in other families with unusually high rates of the disease.

In the study, LoPiccolo noted that the mutation occurs in about 1 in 15,000 people in the US population, but in certain areas of the Southeastern US, it can be as frequent as 1 in 2,000 people.

Lung cancer occurs when abnormal cells grow uncontrollably in the lungs. It remains the leading cause of cancer deaths worldwide, with an estimated 2.5 million new cases and 1.8 million deaths in 2022.

Beyond inherited genetic risk, lung cancer can also develop following exposure to second-hand smoke, air pollution, and workplace chemicals and carcinogens.

These include asbestos, silica dust, diesel exhaust, arsenic and other industrial chemicals.

Radon gas is another lesser-known risk factor. It is invisible and odorless, and prolonged exposure to high levels of radon can increase the risk of lung cancer.

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Lung cancer in people who have never smoked is an increasingly recognized global health concern. A new study found that a rare inherited EGFR mutation may increase lung cancer risk by over 60 times in never-smokers.Lung cancer in never-smokers is the seventh leading cause of cancer death worldwide. Approximately 60% to 80% of lung cancer cases in never-smokers globally occur in females.The study, published in Science, found that a rare inherited EGFR T790M mutation can increase lung cancer risk by over 60 times in never-smokers and 25 times in smokers.Smoking itself increases the risk of developing lung cancer fourfold in the general population.What Did The Study Find?To look for the rare mutation, researchers evaluated genotyping data from 3.37 million people and found that it occurs in about 1 in 15,850 people.Among the 17 cancers and non-pulmonary conditions screened, the mutation showed a strong association only with lung cancer. Researchers also traced its origin to southern Appalachian populations in the US.“Recognition of individuals more likely to carry EGFR T790M, including those with family history of lung cancer, multifocal lung cancer, or lung nodules or Southeastern US ancestry, may help to inform future screening and prevention strategies for those at highest risk,” said the researchers.“Smoking is bad for lung cancer. This mutation is bad for lung cancer. When you do both, your risk is the sum of those two risks,” said Alexander Gusev, a quantitative geneticist at Dana-Farber. “So, you definitely don't want to smoke.”The mutation was not linked to any of the 17 other common cancers studied, suggesting that its effects may be largely limited to lung cancer.Could Genetic Testing Change Lung Cancer Screening?“Today, lung cancer screening is driven almost entirely by smoking history,” said Jaclyn LoPiccolo, attending physician and lung cancer researcher at Dana-Farber Cancer Institute, who co-led the study.LoPiccolo added that the findings raise the possibility that, in the future, screening could also be dictated by inherited genetic risk.“If further studies confirm the benefit, people with EGFR T790M could be identified through genetic testing and offered personalized CT screening to identify lung cancers when they are at their most curable stage,” she said.How Does The Mutation Increase Risk?Although most lung cancers are associated with tobacco use or exposure, the proportion diagnosed in people who have never smoked has been rising. Yet the genetic factors underlying these cancers, particularly the role of inherited risk, are not well understood.In 2005, researchers identified the rare inherited EGFR T790M mutation in a European family with multiple cases of lung cancer. Since then, the mutation has been reported in other families with unusually high rates of the disease.In the study, LoPiccolo noted that the mutation occurs in about 1 in 15,000 people in the US population, but in certain areas of the Southeastern US, it can be as frequent as 1 in 2,000 people.Other Lung Cancer Risk FactorsLung cancer occurs when abnormal cells grow uncontrollably in the lungs. It remains the leading cause of cancer deaths worldwide, with an estimated 2.5 million new cases and 1.8 million deaths in 2022.Beyond inherited genetic risk, lung cancer can also develop following exposure to second-hand smoke, air pollution, and workplace chemicals and carcinogens.These include asbestos, silica dust, diesel exhaust, arsenic and other industrial chemicals.Radon gas is another lesser-known risk factor. It is invisible and odorless, and prolonged exposure to high levels of radon can increase the risk of lung cancer.

never smoked, still got lung cancer? rare mutation linked to over 60x risk

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