A large international study suggests that some people's genes make them more susceptible to lung cancer, which kills Kentuckians at the highest rate in the nation.

The research, published online last week in the respected journal Nature Genetics, came out of the largest genetic study of lung cancer ever conducted. It involved a team from 18 countries, including the United States, and was organized in part by the International Agency for Research on Cancer in Lyon, France.

The study examined genetic variations in 15,000 people -- 6,000 with lung cancer and 9,000 without -- and estimated that two such variations may increase lifetime lung cancer risk by as much as 60 percent.

While doctors say smoking is still the main culprit for lung cancer, researchers said the new findings may help explain why some lifelong smokers don't get lung cancer and some non-smokers do. Both smokers and non-smokers with the genetic variation appear to face increased risk.

"These results give us a better understanding of the disease," said Dr. Paul Brennan, head of the research group at the international cancer agency.

Noting that "treatments for lung cancer are still very poor," Brennan said the new study "will hopefully lead us to better diagnostic and treatment options."

The study is the latest in a growing body of research on genetic ties to various types of malignancies, including breast, ovarian, colorectal and prostate cancers.

Karen Risinger of La Grange, Ky., a 55-year-old lung cancer survivor with a family history of the disease, said she would love to see doctors develop genetic testing for lung cancer, so it can be detected early and perhaps help people avoid the heartache her family has suffered.

Risinger -- who recalls watching her father, a smoker, die of the disease in 1986 at the age of 54 -- was diagnosed six years ago and underwent surgery to remove the top lobe of her right lung.

"Thank God I lived. I have not touched a cigarette since my surgery," said Risinger, a former pack-a-day smoker. Now, she worries about her children, "especially my son, because he is a smoker."

Dr. Goetz Kloecker, director of thoracic oncology at the University of Louisville's James Graham Brown Cancer Center and who was not part of the study, said he hopes the genetic research doesn't obscure the fact that smoking, and to a lesser extent, environmental factors such as radon and secondhand smoke, are the biggest causes of lung cancer.

According to the U.S. Centers for Disease Control and Prevention, smokers are 10 to 20 times more likely to get lung cancer or die from it than people who do not smoke.

"The majority of lung cancer -- 90 percent -- is in one way or the other a result of smoking. ... Smoking is risk No. 1," he said. "If someone smokes and has this gene, it's double jeopardy."

Low survival rate

Lung cancer is by far the biggest cancer killer in America, responsible for almost 162,000 deaths annually -- more than colon, breast and prostate cancers combined.

The disease takes years to develop and is often discovered in its late stages. Despite surgery, chemotherapy and radiation treatments, the five-year survival rate is only about 15 percent.

Risinger attributes her survival partly to chance timing; doctors found her cancer early when she went for a routine checkup and got a chest X-ray because she was a smoker.

A CDC survey shows that 28.2 percent of Kentucky adults smoke, the nation's highest rate. Accordingly, Kentucky has a lung cancer death rate 35 percent higher than the national average for women and 54 percent higher than the national average for men.

Indiana -- where 24.1 percent of adults smoke -- has a death rate 15 percent higher for women and 21 percent higher for men. The American Cancer Society projects the disease will claim 3,990 lives this year in Indiana and 3,480 in Kentucky.

"That's a very sad record," Kloecker said. "What's causing this? Our relationship with tobacco."

For those with genetic susceptibility to lung cancer, tobacco can pose even a greater risk.

A smaller study published in the American Journal of Human Genetics in 2004 suggested that smoking even a small amount can lead to lung cancer for individuals with inherited susceptibility.

That study found evidence of a lung cancer susceptibility gene on chromosome 6 -- a different one than in the later Nature Genetics study, which identified a region on the fifth human chromosome as containing two suspect genes. The most likely, researchers said, is a gene that encodes part of an enzyme called telomerase, which is linked to cancer development.

Any carriers of those genetic variations, including those who have never smoked, showed a risk for cancer.

Still, Kloecker reiterated that genetics play a relatively small role.

"Genetics will not explain Kentucky's high rates," he said.

Other cancers' genetic links

Overall, about 5 percent to 10 percent of cancers of all types are due to "some sort of genetic factors," said Andrea Lewis, a genetic counselor at Norton Cancer Institute.

"It's a very important group," she said. "If we predict, we could intervene and possibly prevent cancer from happening."

Perhaps the most well-known genetic tie involves breast and ovarian cancers, in which people can inherit a predisposition through either parent. Mutations in the genes involved -- BRCA1 and BRCA2 -- are relatively rare and account for a minority of breast cancer cases. But a woman with a mutation faces a 56 percent to 87 percent risk of breast cancer over her lifetime, compared with a 12 percent risk for the average woman.

Genetic testing is now available for breast cancer, and those with the genes can choose surveillance through mammograms and clinical breast exams or more drastic preventive measures such as surgery. Experts suggest they also develop healthier habits by reducing alcohol consumption and exercising more.

Although genetic testing is not currently available for the potential lung cancer susceptibility genes identified in the latest study, doctors said healthy habits are the main key to preventing lung cancer for everyone.

"It's so important never to start smoking," Kloecker said. "Once you have lung cancer, it's a curse -- a death sentence for most people."

Risinger said she realizes how lucky she is. She is now cancer-free and said she feels good; breathing difficulties she faced after the surgery have faded.

"I was blessed," she said.