Every year, 3,500 Kentuckians lose their lives to lung cancer, and smoking has long been blamed as the culprit.
But scientists now say it may not be acting alone.
A growing body of research, including two studies under way at the University of Kentucky, shows the risk of lung cancer is much higher for smokers exposed to carcinogens such as radon, asbestos, arsenic or chromium.
How much higher? If you smoke, your risk of lung cancer is up to 20 times greater than for a nonsmoker - but if you smoke and are also exposed to carcinogens, your risk is up to 300 times greater, studies indicate.
The studies help explain why Kentucky's lung-cancer and death rates are so much higher than for the rest of the nation, specialists say. The state's death rate for the disease is 56 percent higher than the national average - and some Appalachian counties' rates are more than double the national average.
While Kentucky's adult smoking rate of 28 percent is the highest in the nation, it's not enough to account for the state's sky-high lung-cancer rates, they say.
"We in Kentucky have extraordinarily high lung cancer incidence and death rates - the highest in the nation by far - and that can't be explained only by smoking," said Thomas Tucker, who directs the state's cancer registry and is involved in one of the UK studies. "Certainly smoking is part of it. But there are other things too. And figuring this out is not an easy quest."
Kentucky's high levels of carcinogens is one place they're looking.
For example, the U.S. Environmental Protection Agency classifies a wide swath of central Kentucky as having the highest potential for indoor radon gas. And research by Tucker and others has shown high rates of arsenic and chromium in Appalachian residents compared with residents of Jefferson County.
"We're always quick to look to smoking as a plain and simple kind of answer," said Amy Copeland, director of medical outreach for the national advocacy group Lung Cancer Alliance. "But there's still a lot of questions and a lot of things that we don't know."
Evelyn Watkins of Louisville, who was diagnosed with late-stage lung cancer in 2011 and is still being treated, said she's glad researchers are looking deeply into the causes of the deadly disease. Watkins started smoking when she was 16 and said she smoked four packs of cigarettes a day at one point, tapering to one pack a day before quitting cold turkey in 2009.
She also worked in an aluminum factory and was exposed to a mix of chemicals.
"We not only dealt with it; we worked in it like a mist. We were inhaling it," said Watkins, 61, a grandmother of five.
While doctors aren't sure how smoking interacts with such carcinogens in the body, some theorize that when smoking damages lung cells' DNA, the lungs become more susceptible to damage from other toxins.
"There's got to be more going on than just smoking, than just the environment, than just genetics," Arnold said. "It's probably a combination of all three."