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Neversmoker Lung Cancer–A Different Disease

Lung Cancer in Smokers, Nonsmokers May Be a Different Disease

Tumors in people who never smoked had more genetic abnormalities, study says

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

Last Updated: Nov. 09, 2010

Copyright © 2010 HealthDay. All rights reserved.

© 2009 The Bonnie J. Addario Lung Cancer Foundation - A BREATH AWAY FROM THE CURE. All Rights Reserv

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The thing I don't understand in these studies is why it is assumed that a smoker could not also have this genetic EGFR mutation. Smokers also get adenocarcinomas. Maybe I don't understand the science of it, but it doesn't make sense to me that a genetic mutation that predisposes someone to Lung Cancer wouldn't predispose them to it whether or not they took up smoking. Our genes don't know whether or not we're going to smoke. I guess my concern is that they're going to lump people into the 'you have the 'smoking' cancer, so it's obviously NOT a genetic mutation' and 'you have the 'non-smoking' cancer so let's poke around and ask some questions.' Mightn't it be worthwhile to just make it protocol to examine ALL the factors in ALL patients rather than make assumptions? ?Otherwise it seems to me that some people who could be effectively treated targeting a genetic mutation are going to get missed.

Again... Maybe I just don't get the science.

Incidentally--this genetic mutation stuff is fascinating and not just when talking about LC. It amazes me that things that have been assumed 'just couldn't be genetic' are being found to be that way at an increasing rate. I hope that as more is learned doctors won't just summarily shut the door on a genetic possibility. That's something I'm dealing with right now with my 'other' issues, and I'm so glad that I'm able to get treated somewhere where ALL factors are considered.

Sorry. Just thinking out loud.

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Highly recommend thinking outloud. Do it all the time.

This is not all such a new idea. Some doctors for years have assumed SCLC was the smokers cancer and NSCLC Adenocarcinoma was the non-smokers cancer. When I got the call telling me they'd found cancer cells in the fluid from my pleural effusion, the doctors said "it was not smokers cancer. I had smoked for years. It was, in fact, NSCLC adenocarcinoma. Danger I see here is shifting what little research monies there is for LC to the group that public opinion considers didn't cause their own cancer.

Thanks Randy.

Judy in KW

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Great article. Thanks for posting it. I too was told the type of cancer I had was not normal for smokers. Is there a normal :?: I wonder if this means they won't research cancer in smokers once they distinquish the difference between smokers and non-smokers!

Thanks Randy :D


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