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Lung Cancer in Smokers, Nonsmokers May Be a Different Disease
Date:11/9/2010

By Jenifer Goodwin
HealthDay Reporter

MONDAY, Nov. 8 (HealthDay News) -- New research suggests that lung cancer in people who have never smoked may be a different disease than it is in smokers.

Scientists compared the genetic characteristics of lung cancer tumors in 30 people who never smoked to tumors in 53 smokers or former smokers.

The tumors of people who had never smoked had twice as many DNA abnormalities as people who were current or former smokers, said study author Kelsie Thu, a doctoral candidate at the British Columbia Cancer Research Centre in Vancouver.

"This is suggesting there might be something different going on with tumors in never-smokers," Thu said. "If we find out lung cancer in never-smokers is a different disease and we can identify what those differences are, maybe we can design specific therapies that target the genetic alterations in never-smokers and improve the prognosis."

The study was to be presented Monday at the American Association of Cancer Research's annual conference, in Philadelphia.

Lung cancer is the leading cause of cancer deaths in the United States for men and woman, according to the American Cancer Society. Lung cancer will kill an estimated 157,000 Americans this year.

But it's not just smokers who get it -- lung cancer is the seventh-leading cause of cancer deaths among people who have never smoked, Thu said. Dana Reeve, wife of the late Christopher Reeve, died in 2006 at age 44 from lung cancer. She had never smoked.

Prior research has hinted that lung cancer tumors in never-smokers is different than the tumors in smokers. Compared to former and current smokers with lung cancer, never-smokers with lung cancer tend to be diagnosed younger, are more likely to be women and are more likely to have adenocarcinomas, the most common type of cancer. All of the lung cancer patients in the study had adenocarcinoma.

People who never smoked are also more likely to have a mutation in the epidermal growth factor receptor (EGFR) gene.

"All of those differences are evidence there may be something different going on with their tumors," Thu said.

The new study confirmed earlier findings that nonsmokers were more likely to have the EGFR mutation, Thu said.

Never-smokers with lung cancer were also less likely to have the KRAS mutation, which has also been shown in prior research.

In smokers, it's believed that the carcinogens in tobacco and cigarettes cause DNA mutations that lead to the uncontrolled growth of cancer cells, Thu said.

In nonsmokers, the added genetic mutations suggest other mechanisms are driving the tumor growth, Thu said. "We hypothesize there is more genomic instability in the never-smokers than the smokers, and that leads us to believe there may be some other molecular mechanism that is driving the tumor development," she said.

Dr. David Carbone, a professor of medicine and cancer biology at Vanderbilt University, said the new study supports the idea that cancer in people who've never smoked vs. current and former smokers is different.

In never-smokers, the challenge is not only coming up with treatments that target the genetic mutations of their tumor, but in identifying people soon enough to help them, said Carbone, a member of the Lung Cancer Foundation of America's scientific advisory board.

Nonsmokers tend to take longer to be diagnosed with lung cancer because few suspect they have it, he said.

"We often see never-smokers present with advanced, incurable disease," he said.

Drugs that target particular genetic pathways have been very successful. Erlotinib (Tarceva), for example, has been shown to extend the lives of lung cancer patients with the EGFR mutation, present in about 10 percent of lung cancers, Carbone said.

More information

The U.S. National Cancer Institute has more on lung cancer.

SOURCES: Kelsie Thu, Ph.D. candidate, British Columbia Cancer Research Center, Vancouver; David Carbone, M.D., Ph.D., professor, medicine and cancer biology, Vanderbilt University School of Medicine, Nashville, Tenn.; Nov. 8, 2010, presentation, American Association of Cancer Research Frontiers in Cancer Prevention annual conference, Philadelphia


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