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Genetic risk adds to dangers of smoking

Though lung cancer is the leading cause of cancer deaths worldwide, scientists have identified few genetic risk factors for the disease. “Only 10 percent of smokers will develop lung cancer in their lifetime, and genetic testing to determine the population of smokers who are most predisposed to develop the disease is needed,” says Joanne B. Weidhaas, M.D., Ph.D., assistant professor of therapeutic radiology.

Weidhaas and Frank Slack, Ph.D., associate professor of molecular, cellular and developmental biology at Yale, had previously shown that the microRNA let-7, a snippet of genetic material that puts the brakes on cell proliferation—a process that runs rampant in cancer—could significantly reduce lung cancer in mice.

In a study published in the October 15 issue of Cancer Research, Weidhaas, Slack and colleagues discovered a genetic variation in a let-7 target gene that greatly reduces let-7’s protective effect.

The newly identified variation, which compromises let-7’s regulation of a cancer-associated gene called KRAS, was found in 5.8 percent of a sample of world populations, but in 20 percent of patients with non-small cell lung cancer (NSCLC); the researchers estimate that moderate smokers carrying the variation are 1.4 to 2.3 times as likely to develop NSCLC.