A rare inherited gene variant, more common in parts of Southern Appalachia, raised lung cancer risk 25-fold in a 3.3 million-person study.

Here's a study worth reading carefully, especially if your family tree has roots in the mountains. Researchers led by Dana-Farber Cancer Institute and the 23andMe Research Institute analyzed data from more than 3.3 million people and found that a rare inherited mutation, EGFR T790M, raised the risk of lung cancer 25 times, Fox News reports on the study, published in the journal Science. Among people who had never smoked, carriers had about 62 times the odds of lung cancer compared with never-smokers without it. The variant showed no increased risk across 17 other cancers studied. It's rare, roughly one in 15,000 to 16,000 people nationwide, but researchers estimate as many as one in 2,000 may carry it in parts of Southern Appalachia, and most U.S. carriers trace back to British and Irish settlers there about 200 to 225 years ago. "Today, lung cancer screening is driven almost entirely by smoking history," said co-author Jaclyn LoPiccolo, who suggested inherited risk could someday help guide screening if further studies confirm the benefit. "To my knowledge, it's one of the strongest, if not the strongest, cancer risk-increasing mutations that has ever been found," said Dana-Farber geneticist Alexander Gusev. Now the caveats. The study shows a strong association, not proof that genetic testing improves survival. Because the variant is so rare, researchers found relatively few carriers even among millions of participants, so the exact size of the risk is uncertain. The analysis also relied heavily on 23andMe research participants, who may not represent the broader population. So what should you do? The researchers suggest that people with a strong family history of lung cancer, multiple lung nodules or tumors, or family roots in parts of the southeastern U.S. consider talking with a genetic counselor about whether testing or screening makes sense. And if you smoke, Gusev put it plainly: "So, you definitely don't want to smoke."