People with this gene smoke longer, get cancer sooner

"Although it's clear the gene increases the chances a person will develop lung cancer at a younger age, it also is clear that the risk can be reversed with treatment," says Li-Shiun Chen. (Credit: SuperFantastic/Flickr)

Smokers with a specific genetic variation are more likely to keep smoking longer than those who don’t have it new research indicates. They’re also more likely to be diagnosed with lung cancer at a younger age.

The findings potentially could change how patients are screened for lung cancer.

“People with the risk variant average a four-year delay in the age at which they quit smoking,” says first author Li-Shiun Chen, instructor of psychiatry at Washington University in St. Louis. “Instead of quitting at age 52, which was the average age when study participants with a normal gene stopped smoking, people with the genetic variant quit at age 56.”

Risk reversal

For a new study, published in the Journal of the National Cancer Institute, researchers analyzed 24 studies involving more than 29,000 smokers of European ancestry and found that smokers with a particular variation in the CHRNA5 gene, a nicotine receptor, are more likely to continue smoking for four years after those without the variant had quit. They are also more likely to be diagnosed with lung cancer four years earlier.

Those with the gene variant also tend to inhale more deeply when they smoke. That combination of genes and behavior contributes to the development of lung cancer earlier in life.

“They are likely to be diagnosed four years earlier,” she says. “In those with lung cancer, the average smoker without the gene variant is diagnosed at age 65. Those with the greater genetic risk tend to be diagnosed at 61.”

The presence of the gene variation has important clinical implications. Smokers who have the gene variant could undergo lung cancer screening at a younger age, Chen says. Previous work shows that those with the gene variant are more likely to respond to medications that help people quit smoking, so knowing more about a smoker’s genetic makeup could help guide that individual’s therapy.

“The same people with this high-risk gene are more likely to respond to smoking-cessation medications, such as nicotine-replacement patches, lozenges, or gum,” Chen says. “Although it’s clear the gene increases the chances a person will develop lung cancer at a younger age, it also is clear that the risk can be reversed with treatment.”

Earlier the better

Lung cancer is the most common cancer worldwide, making up 13 percent of all cancer cases and leading to 27 percent of all cancer deaths. And survival rates are low. About half of all lung cancer patients die within a year of being diagnosed. Only about one in six are still alive five years after diagnosis.

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“So a diagnosis that comes four years earlier is very significant clinically,” Chen says.

The clinical implications of the findings are enormous, says senior investigator Laura Jean Bierut, professor of psychiatry. Currently, people tend to be screened for lung cancer according to how much they smoke and how old they are. But the new research supports the idea of doctors using genetic information to target people who might not be screened otherwise.

“Adding this information to screening criteria could help us focus our resources on people at the highest risk. In addition, knowing that they are the ones most likely to respond to nicotine-replacement therapy could allow us to respond with treatments that are more likely to be effective.”

The researchers plan to expand their studies to include smokers from ethnic groups not represented in this analysis. They also want to look at other genes related to smoking, nicotine dependence and cancer risk, with the goal of creating a risk score that could be used to assess addiction and cancer risk in individual smokers.

The National Cancer Institute, the National Human Genome Research Institute, the National Institute on Drug Abuse, the National Heart, Lung and Blood Institute, and the National Center for Research Resources of the National Institutes of Health funded the work.

Source: Washington University in St. Louis