Mon Jun 30, 2008 11:17am EDT
By Maggie Fox, Health and Science Editor
WASHINGTON (Reuters) - A drug developed using nanotechnology and a fungus that contaminated a lab experiment may be broadly effective against a range of cancers, U.S. researchers reported on Sunday.
The drug, called lodamin, was improved in one of the last experiments overseen by Dr. Judah Folkman, a cancer researcher who died in January. Folkman pioneered the idea of angiogenesis therapy -- starving tumors by preventing them from growing blood supplies.
Lodamin is an angiogenesis inhibitor that Folkman's team has been working to perfect for 20 years. Writing in the journal Nature Biotechnology, his colleagues say they developed a formulation that works as a pill, without side-effects.
They have licensed it to SynDevRx, Inc, a privately held Cambridge, Massachusetts biotechnology company that has recruited several prominent cancer experts to its board.
Tests in mice showed it worked against a range of tumors, including breast cancer, neuroblastoma, ovarian cancer, prostate cancer, brain tumors known as glioblastomas and uterine tumors.
It helped stop so-called primary tumors and also prevented their spread, Ofra Benny of Children's Hospital Boston and Harvard Medical School and colleagues reported.
"Using the oral route of administration, it first reaches the liver, making it especially efficient in preventing the development of liver metastasis in mice," they wrote in their report. "Liver metastasis is very common in many tumor types and is often associated with a poor prognosis and survival rate," they added.
'ALMOST CLEAN' LIVERS
"When I looked at the livers of the mice, the treated group was almost clean," Benny said in a statement. "In the control group you couldn't recognize the livers -- they were a mass of tumors."
The drug was known experimentally as TNP-470, and was originally isolated from a fungus called Aspergillus fumigatus fresenius.
Harvards's Donald Ingber discovered the fungus by accident while trying to grow endothelial cells -- the cells that line blood vessels. The mold affected the cells in a way known to prevent the growth of tiny blood vessels known as capillaries.
Ingber and Folkman developed TNP-470 with the help of Takeda Chemical Industries in Japan in 1990.
But the drug affected the brain, causing depression, dizziness and other side-effects. It also did not stay in the body long and required constant infusions. The lab dropped it.
Efforts to improve it did not work well. Then Benny and colleagues tried nanotechnology, attaching two "pom-pom"-shaped polymers to TNP-470, protecting it from stomach acid.
In mice, the altered drug, now named lodamin, went straight to tumor cells and helped suppress melanoma and lung cancer, with no apparent side effects, Benny said.
All untreated mice had fluid in the abdominal cavity, and enlarged livers covered with tumors. Mice treated with lodamin had normal-looking livers and spleens, the researchers said.
Twenty days after being injected with cancer cells, four out of seven untreated mice had died, while all treated mice were still alive, Benny's team reported.
"I had never expected such a strong effect on these aggressive tumor models," she said. The researchers believe lodamin may also be useful in other diseases marked by abnormal blood vessel growth, such as age-related macular degeneration.
(Editing by Todd Eastham)
Monday, June 30, 2008
Tuesday, June 10, 2008
Smoking causes middle-age mental decline
Lighting up affects mind as well as body, new study shows
updated 4:38 p.m. ET, Mon., June. 9, 2008
CHICAGO - Middle-aged adults who smoke tended to perform poorly on tests of memory and reasoning compared to nonsmokers, adding to the list of reasons not to smoke, French researchers said on Monday.
Analyzing previously collected data on about 5,000 British civil servants, the researchers found those who smoked were more likely than people who never smoked to be in the lowest-performing of five groups in tests of memory, reasoning, vocabulary and verbal fluency.
Smoking was associated with mental decline in middle age, as it is with dementia and a host of physical ills later in life, they found.
"Smoking in middle age is associated with memory deficit and decline in reasoning abilities," concluded Severine Sabia and colleagues from the National Institute of Health and Medical Research in Villejuif, France.
Compared to smokers, people who said they had quit cigarettes were more likely to adopt healthier behaviors, such as drinking less alcohol, being more physically active, and eating more fruits and vegetables, Sabia reported in the journal Archives of Internal Medicine.
The participants were aged 35 to 55 at the beginning of the study, which followed some subjects up to 17 years.
The study also demonstrated how difficult it can be to conduct long-term research on smokers: more than twice as many smokers as non-smokers refused to take the memory test again or were not able to be re-tested, in some cases because they died in the interim.
Copyright 2008 Reuters.
updated 4:38 p.m. ET, Mon., June. 9, 2008
CHICAGO - Middle-aged adults who smoke tended to perform poorly on tests of memory and reasoning compared to nonsmokers, adding to the list of reasons not to smoke, French researchers said on Monday.
Analyzing previously collected data on about 5,000 British civil servants, the researchers found those who smoked were more likely than people who never smoked to be in the lowest-performing of five groups in tests of memory, reasoning, vocabulary and verbal fluency.
Smoking was associated with mental decline in middle age, as it is with dementia and a host of physical ills later in life, they found.
"Smoking in middle age is associated with memory deficit and decline in reasoning abilities," concluded Severine Sabia and colleagues from the National Institute of Health and Medical Research in Villejuif, France.
Compared to smokers, people who said they had quit cigarettes were more likely to adopt healthier behaviors, such as drinking less alcohol, being more physically active, and eating more fruits and vegetables, Sabia reported in the journal Archives of Internal Medicine.
The participants were aged 35 to 55 at the beginning of the study, which followed some subjects up to 17 years.
The study also demonstrated how difficult it can be to conduct long-term research on smokers: more than twice as many smokers as non-smokers refused to take the memory test again or were not able to be re-tested, in some cases because they died in the interim.
Copyright 2008 Reuters.
Tuesday, June 3, 2008
Antibacterial wipes can spread superbugs: study
Tue Jun 3, 2008 1:11pm EDT
By Michael Kahn
LONDON (Reuters) - Disinfectant wipes routinely used in hospitals may actually spread drug-resistant bacteria rather than kill the dangerous infections, British researchers said on Tuesday.
While the wipes killed some bacteria, a study of two hospitals showed they did not get them all and could transfer the so-called superbugs to other surfaces, Gareth Williams, a microbiologist at Cardiff University, said.
The findings presented at the American Society of Microbiology's General Meeting in Boston focused on bacteria that included methicillin-resistant Staphylococcus aureus, or MRSA.
"What we have found is there is a high risk," Williams, who led the study, said by telephone. "We need to give guidance to the staff on how to use the wipes because we found there is a possibility of cross transfer."
MRSA infections can range from boils to more severe infections of the bloodstream, lungs and surgical sites. Most cases are associated with hospitals, nursing homes or other health care facilities.
The superbug can cause life-threatening and disfiguring infections and can often only be treated with expensive, intravenous antibiotics.
Experts have been saying for years that poor hospital practices spread dangerous bacteria, and yet many studies have shown that health care workers, including doctors and nurses, often fail to even wash their hands as directed.
The findings from a study of intensive care units at two Welsh hospitals suggest that even cleaning with antimicrobial wipes may not be enough depending on how staff use them.
The researchers found that many health care workers cleaned multiple surfaces near patients, such as bed rails, monitors and tables with a single wipe and risked sweeping the infections around rather than cleaning them up.
"We found that the most effective way to prevent the risk of MRSA spread in hospital wards is to ensure the wipe is used only once on one surface," Williams said.
By Michael Kahn
LONDON (Reuters) - Disinfectant wipes routinely used in hospitals may actually spread drug-resistant bacteria rather than kill the dangerous infections, British researchers said on Tuesday.
While the wipes killed some bacteria, a study of two hospitals showed they did not get them all and could transfer the so-called superbugs to other surfaces, Gareth Williams, a microbiologist at Cardiff University, said.
The findings presented at the American Society of Microbiology's General Meeting in Boston focused on bacteria that included methicillin-resistant Staphylococcus aureus, or MRSA.
"What we have found is there is a high risk," Williams, who led the study, said by telephone. "We need to give guidance to the staff on how to use the wipes because we found there is a possibility of cross transfer."
MRSA infections can range from boils to more severe infections of the bloodstream, lungs and surgical sites. Most cases are associated with hospitals, nursing homes or other health care facilities.
The superbug can cause life-threatening and disfiguring infections and can often only be treated with expensive, intravenous antibiotics.
Experts have been saying for years that poor hospital practices spread dangerous bacteria, and yet many studies have shown that health care workers, including doctors and nurses, often fail to even wash their hands as directed.
The findings from a study of intensive care units at two Welsh hospitals suggest that even cleaning with antimicrobial wipes may not be enough depending on how staff use them.
The researchers found that many health care workers cleaned multiple surfaces near patients, such as bed rails, monitors and tables with a single wipe and risked sweeping the infections around rather than cleaning them up.
"We found that the most effective way to prevent the risk of MRSA spread in hospital wards is to ensure the wipe is used only once on one surface," Williams said.
Celebrex Shows Promise in Lung Cancer Prevention
By Julie Steenhuysen
Reuters
CHICAGO
A high dose of the arthritis drug Celebrex showed early signs that it may help prevent lung cancer in heavy smokers, U.S. researchers said on Sunday.
The Pfizer Inc drug, also known as celecoxib, works by blocking the COX-2 enzyme that causes inflammation, which has been linked with cancer.
A six-month study of 212 current or heavy smokers found a reduction in a specific type of precancerous change in lung cells in people who took a high dose of Celebrex compared with those who took a placebo.
None of the study participants had any heart-related problems such as those with Merck & Co Inc's now withdrawn arthritis drug Vioxx, another COX-2 inhibitor.
"Celebrex was safe and we did not see any cardiovascular events," said Dr. Edward Kim of M.D. Anderson Cancer Center in Houston, who presented his findings at a meeting of the American Society of Clinical Oncology in Chicago.
He said the study suggests that a high dose of Celebrex might alter some of the cellular changes that lead up to lung cancer. But the finding is very early and would need to be confirmed in longer, larger studies.
"This is not a study where we go tell someone who is a heavy smoker to start taking Celebrex to prevent lung cancer," Kim said in an interview.
Lung cancer is the leading cause of cancer death in the United States, according to the American Cancer Society. In 2008, about 215,000 people will be diagnosed with lung cancer and about 114,000 people will die from it.
The study was started before news emerged in September 2004 that Vioxx doubled the risk of heart attack and stroke in certain patients.
Kim said the trial was put on hold in December 2004 at the request of Pfizer and the National Cancer Institute, which funded the trial, so the researchers could look for signs of heart attacks or strokes.
It was started up again in May 2005 after the researchers added safeguards, including consultations with cardiologists, to reduce heart risks.
EARLY SIGNS
Rather than a direct measure of cancer prevention, which could take many years, Kim said the researchers were looking for early changes in the body that might suggest the drug could reduce the chances of developing lung cancer.
Two large, long-running lung cancer prevention studies of beta-carotene and vitamin A supplements found they actually increased the risk of lung cancer.
"We have not had positive results with these studies. Now we would like to search for an intermediate endpoint or biomarker," Kim said at a media briefing.
"Perhaps that will lead us in the direction of who we need to target in the future," he said.
The researchers tested Celebrex in the study because studies in cells, mice and in people have shown the COX-2 enzyme is present at higher than normal levels in lung cancer and in precancerous lesions of the lung, Kim said. COX-2 is thought to play a role in the development of blood vessels that feed tumors.
Kim's study measured levels of the Ki-67 protein, a marker for cell growth. The researchers wanted to see if Celebrex had an impact on levels of this protein in tissue samples taken from the lungs of heavy smokers.
At the beginning of the study, the researchers took lung samples from six predetermined areas of the lung.
People in the study either got a 200 milligram or a 400 milligram dose of Celebrex twice a day, or a placebo.
After three months, they took more lung samples, and they took samples again at six months. Kim said the group that got the higher dose of Celebrex saw a reduction in levels of the Ki-67 protein.
Kim said it will be important to find better ways of identifying people who are at the highest risk for lung cancer for whom the benefits of taking a high-dose COX-2 inhibitor would outweigh any potential heart risks.
Reuters
CHICAGO
A high dose of the arthritis drug Celebrex showed early signs that it may help prevent lung cancer in heavy smokers, U.S. researchers said on Sunday.
The Pfizer Inc drug, also known as celecoxib, works by blocking the COX-2 enzyme that causes inflammation, which has been linked with cancer.
A six-month study of 212 current or heavy smokers found a reduction in a specific type of precancerous change in lung cells in people who took a high dose of Celebrex compared with those who took a placebo.
None of the study participants had any heart-related problems such as those with Merck & Co Inc's now withdrawn arthritis drug Vioxx, another COX-2 inhibitor.
"Celebrex was safe and we did not see any cardiovascular events," said Dr. Edward Kim of M.D. Anderson Cancer Center in Houston, who presented his findings at a meeting of the American Society of Clinical Oncology in Chicago.
He said the study suggests that a high dose of Celebrex might alter some of the cellular changes that lead up to lung cancer. But the finding is very early and would need to be confirmed in longer, larger studies.
"This is not a study where we go tell someone who is a heavy smoker to start taking Celebrex to prevent lung cancer," Kim said in an interview.
Lung cancer is the leading cause of cancer death in the United States, according to the American Cancer Society. In 2008, about 215,000 people will be diagnosed with lung cancer and about 114,000 people will die from it.
The study was started before news emerged in September 2004 that Vioxx doubled the risk of heart attack and stroke in certain patients.
Kim said the trial was put on hold in December 2004 at the request of Pfizer and the National Cancer Institute, which funded the trial, so the researchers could look for signs of heart attacks or strokes.
It was started up again in May 2005 after the researchers added safeguards, including consultations with cardiologists, to reduce heart risks.
EARLY SIGNS
Rather than a direct measure of cancer prevention, which could take many years, Kim said the researchers were looking for early changes in the body that might suggest the drug could reduce the chances of developing lung cancer.
Two large, long-running lung cancer prevention studies of beta-carotene and vitamin A supplements found they actually increased the risk of lung cancer.
"We have not had positive results with these studies. Now we would like to search for an intermediate endpoint or biomarker," Kim said at a media briefing.
"Perhaps that will lead us in the direction of who we need to target in the future," he said.
The researchers tested Celebrex in the study because studies in cells, mice and in people have shown the COX-2 enzyme is present at higher than normal levels in lung cancer and in precancerous lesions of the lung, Kim said. COX-2 is thought to play a role in the development of blood vessels that feed tumors.
Kim's study measured levels of the Ki-67 protein, a marker for cell growth. The researchers wanted to see if Celebrex had an impact on levels of this protein in tissue samples taken from the lungs of heavy smokers.
At the beginning of the study, the researchers took lung samples from six predetermined areas of the lung.
People in the study either got a 200 milligram or a 400 milligram dose of Celebrex twice a day, or a placebo.
After three months, they took more lung samples, and they took samples again at six months. Kim said the group that got the higher dose of Celebrex saw a reduction in levels of the Ki-67 protein.
Kim said it will be important to find better ways of identifying people who are at the highest risk for lung cancer for whom the benefits of taking a high-dose COX-2 inhibitor would outweigh any potential heart risks.
Celebrex Shows Promise in Lung Cancer Prevention
By Julie Steenhuysen
Reuters
CHICAGO
A high dose of the arthritis drug Celebrex showed early signs that it may help prevent lung cancer in heavy smokers, U.S. researchers said on Sunday.
The Pfizer Inc drug, also known as celecoxib, works by blocking the COX-2 enzyme that causes inflammation, which has been linked with cancer.
A six-month study of 212 current or heavy smokers found a reduction in a specific type of precancerous change in lung cells in people who took a high dose of Celebrex compared with those who took a placebo.
None of the study participants had any heart-related problems such as those with Merck & Co Inc's now withdrawn arthritis drug Vioxx, another COX-2 inhibitor.
"Celebrex was safe and we did not see any cardiovascular events," said Dr. Edward Kim of M.D. Anderson Cancer Center in Houston, who presented his findings at a meeting of the American Society of Clinical Oncology in Chicago.
He said the study suggests that a high dose of Celebrex might alter some of the cellular changes that lead up to lung cancer. But the finding is very early and would need to be confirmed in longer, larger studies.
"This is not a study where we go tell someone who is a heavy smoker to start taking Celebrex to prevent lung cancer," Kim said in an interview.
Lung cancer is the leading cause of cancer death in the United States, according to the American Cancer Society. In 2008, about 215,000 people will be diagnosed with lung cancer and about 114,000 people will die from it.
The study was started before news emerged in September 2004 that Vioxx doubled the risk of heart attack and stroke in certain patients.
Kim said the trial was put on hold in December 2004 at the request of Pfizer and the National Cancer Institute, which funded the trial, so the researchers could look for signs of heart attacks or strokes.
It was started up again in May 2005 after the researchers added safeguards, including consultations with cardiologists, to reduce heart risks.
EARLY SIGNS
Rather than a direct measure of cancer prevention, which could take many years, Kim said the researchers were looking for early changes in the body that might suggest the drug could reduce the chances of developing lung cancer.
Two large, long-running lung cancer prevention studies of beta-carotene and vitamin A supplements found they actually increased the risk of lung cancer.
"We have not had positive results with these studies. Now we would like to search for an intermediate endpoint or biomarker," Kim said at a media briefing.
"Perhaps that will lead us in the direction of who we need to target in the future," he said.
The researchers tested Celebrex in the study because studies in cells, mice and in people have shown the COX-2 enzyme is present at higher than normal levels in lung cancer and in precancerous lesions of the lung, Kim said. COX-2 is thought to play a role in the development of blood vessels that feed tumors.
Kim's study measured levels of the Ki-67 protein, a marker for cell growth. The researchers wanted to see if Celebrex had an impact on levels of this protein in tissue samples taken from the lungs of heavy smokers.
At the beginning of the study, the researchers took lung samples from six predetermined areas of the lung.
People in the study either got a 200 milligram or a 400 milligram dose of Celebrex twice a day, or a placebo.
After three months, they took more lung samples, and they took samples again at six months. Kim said the group that got the higher dose of Celebrex saw a reduction in levels of the Ki-67 protein.
Kim said it will be important to find better ways of identifying people who are at the highest risk for lung cancer for whom the benefits of taking a high-dose COX-2 inhibitor would outweigh any potential heart risks.
Reuters
CHICAGO
A high dose of the arthritis drug Celebrex showed early signs that it may help prevent lung cancer in heavy smokers, U.S. researchers said on Sunday.
The Pfizer Inc drug, also known as celecoxib, works by blocking the COX-2 enzyme that causes inflammation, which has been linked with cancer.
A six-month study of 212 current or heavy smokers found a reduction in a specific type of precancerous change in lung cells in people who took a high dose of Celebrex compared with those who took a placebo.
None of the study participants had any heart-related problems such as those with Merck & Co Inc's now withdrawn arthritis drug Vioxx, another COX-2 inhibitor.
"Celebrex was safe and we did not see any cardiovascular events," said Dr. Edward Kim of M.D. Anderson Cancer Center in Houston, who presented his findings at a meeting of the American Society of Clinical Oncology in Chicago.
He said the study suggests that a high dose of Celebrex might alter some of the cellular changes that lead up to lung cancer. But the finding is very early and would need to be confirmed in longer, larger studies.
"This is not a study where we go tell someone who is a heavy smoker to start taking Celebrex to prevent lung cancer," Kim said in an interview.
Lung cancer is the leading cause of cancer death in the United States, according to the American Cancer Society. In 2008, about 215,000 people will be diagnosed with lung cancer and about 114,000 people will die from it.
The study was started before news emerged in September 2004 that Vioxx doubled the risk of heart attack and stroke in certain patients.
Kim said the trial was put on hold in December 2004 at the request of Pfizer and the National Cancer Institute, which funded the trial, so the researchers could look for signs of heart attacks or strokes.
It was started up again in May 2005 after the researchers added safeguards, including consultations with cardiologists, to reduce heart risks.
EARLY SIGNS
Rather than a direct measure of cancer prevention, which could take many years, Kim said the researchers were looking for early changes in the body that might suggest the drug could reduce the chances of developing lung cancer.
Two large, long-running lung cancer prevention studies of beta-carotene and vitamin A supplements found they actually increased the risk of lung cancer.
"We have not had positive results with these studies. Now we would like to search for an intermediate endpoint or biomarker," Kim said at a media briefing.
"Perhaps that will lead us in the direction of who we need to target in the future," he said.
The researchers tested Celebrex in the study because studies in cells, mice and in people have shown the COX-2 enzyme is present at higher than normal levels in lung cancer and in precancerous lesions of the lung, Kim said. COX-2 is thought to play a role in the development of blood vessels that feed tumors.
Kim's study measured levels of the Ki-67 protein, a marker for cell growth. The researchers wanted to see if Celebrex had an impact on levels of this protein in tissue samples taken from the lungs of heavy smokers.
At the beginning of the study, the researchers took lung samples from six predetermined areas of the lung.
People in the study either got a 200 milligram or a 400 milligram dose of Celebrex twice a day, or a placebo.
After three months, they took more lung samples, and they took samples again at six months. Kim said the group that got the higher dose of Celebrex saw a reduction in levels of the Ki-67 protein.
Kim said it will be important to find better ways of identifying people who are at the highest risk for lung cancer for whom the benefits of taking a high-dose COX-2 inhibitor would outweigh any potential heart risks.
Genetic Link Tied to Smoking Addiction
Teams of Scientists Find Genetic Changes Linked to Cigarette Addiction, Lung Cancer
By SETH BORENSTEIN
The Associated Press
WASHINGTON
Scientists have pinpointed genetic variations that make people more likely to get hooked on cigarettes and more prone to develop lung cancer — a finding that could someday lead to screening tests and customized treatments for smokers trying to kick the habit.
The discovery by three separate teams of scientists makes the strongest case so far for the biological underpinnings of nicotine addiction and sheds more light on how genetics and lifestyle habits join forces to cause cancer.
"This is kind of a double whammy gene," said Christopher Amos, a professor of epidemiology at the M.D. Anderson Cancer Center in Houston and author of one of the studies. "It also makes you more likely to be dependent on smoking and less likely to quit smoking."
A smoker who inherits these genetic variations from both parents has an 80 percent greater chance of lung cancer than a smoker without the variants, the researchers reported. And that same smoker on average lights up two extra cigarettes a day and has a much harder time quitting than smokers who don't have these genetic differences.
The researchers disagreed on whether the variants directly increased the risk of lung cancer or did so indirectly, by causing more smoking.
The three studies, funded by governments in the U.S. and Europe, are being published Thursday in the journals Nature and Nature Genetics.
The scientists studied the genes of more than 35,000 white people of European descent in Europe, Canada and the United States. Blacks and Asians will be studied soon and may yield different results, scientists said.
They aren't quite sure if what they found is a set of variations in one gene or in three closely connected genes.
The gene variations, which govern nicotine receptors on cells, could eventually help explain some of the mysteries of chain smoking, nicotine addiction and lung cancer. These oddities include why there are 90-year-old smokers who don't get cancer and people who light up an occasional cigarette and don't get hooked.
"This is really telling us that the vulnerability to smoking and how much you smoke is clearly biologically based," said psychiatry professor Dr. Laura Bierut of Washington University in St. Louis, a genetics and smoking expert who did not take part in the studies. She praised the research as "very intriguing."
The smoking rate among U.S. adults has dropped from 42 percent in 1965 to less than 21 percent now.
The new studies are surprising in that they point to areas of the genetic code that are not associated with pleasure and the rewards of addiction.
That may help explain why some people can quit and others fail, said Dr. Nora Volkow, director of the National Institute of Drug Abuse in Bethesda, Md., which funded one of the studies.
"It opens our eyes," Volkow said Wednesday. "Not everyone takes drugs for the same reason. Not everyone smokes cigarettes for the same reasons."
One clue is in the location of the just-discovered variants, on the long arm of chromosome 15, Volkow said. It is in an area that, when damaged during tests on animals, makes them depressed and anxious. While some people smoke because it helps them focus or gives them a physiological reward, others do it to stave off depression.
That suggests that adding antidepressants to some smokers' treatment could help them kick the habit.
Bierut said a simple, inexpensive test could be developed to screen people for the variants. Kari Stefansson, lead author of the largest of the three studies, agreed. He is chief executive of deCode Genetics of Iceland, which already does prostate cancer genetic tests.
Such testing could carry risks all its own, bioethicist Arthur Caplan of the University of Pennsylvania warned. People who have been found to have a genetic predisposition to addiction and lung cancer could find it harder to get health or life insurance, or their employer might drop their coverage, he said.
"The good news is that getting these risk estimates will help focus anti-smoking campaigns, and some people will want to voluntarily get into anti-addiction programs early, where they will probably work better," Caplan said in an e-mail. But if such testing is done, it should be voluntary, and the results should be kept private, he said.
Smoking-related diseases worldwide kill about one in 10 adults, according to the World Health Organization.
Among the findings:
— Smokers who get the set of variants from only one parent see a risk of lung cancer that is about one-third higher than that of people without the variants. They also smoke about one more cigarette a day on average than other smokers. This group makes up about 45 percent of the population studied.
— Smokers who inherit the variants from both parents have nearly a 1-in-4 chance of developing lung cancer. Their cancer risk is 70 to 80 percent higher than that of smokers without the genetic variants. They smoke on average two extra cigarettes a day. This group accounts for about one in nine people of European descent.
— Smokers who don't have the variants are still more than 10 times more likely to get lung cancer than nonsmokers. Smokers without the variant have about a 14 percent risk of getting lung cancer. The risk of lung cancer for people who have never smoked is less than 1 percent, said another study author, Paul Brennan of the International Agency for Research on Cancer in Lyon, France.
Brennan and Amos, working on different teams, linked the genetic variation itself — when triggered by smoking — directly to lung cancer. Brennan said the nicotine receptors that the variants act on also can stimulate tumor growth.
But Stefansson said the increased lung cancer risk was indirect — the variants led to more smoking, which led to more cancer.
For Stefansson, the research hits home. His father, a smoker, died of lung cancer. And Stefansson, who doesn't smoke, frequently lectures his 23-year-old daughter "who smokes like a chimney." She acts as if she is immortal and smoking can't kill her, Stefansson said. But his own research shows that her genes are probably stacked against her.
———
By SETH BORENSTEIN
The Associated Press
WASHINGTON
Scientists have pinpointed genetic variations that make people more likely to get hooked on cigarettes and more prone to develop lung cancer — a finding that could someday lead to screening tests and customized treatments for smokers trying to kick the habit.
The discovery by three separate teams of scientists makes the strongest case so far for the biological underpinnings of nicotine addiction and sheds more light on how genetics and lifestyle habits join forces to cause cancer.
"This is kind of a double whammy gene," said Christopher Amos, a professor of epidemiology at the M.D. Anderson Cancer Center in Houston and author of one of the studies. "It also makes you more likely to be dependent on smoking and less likely to quit smoking."
A smoker who inherits these genetic variations from both parents has an 80 percent greater chance of lung cancer than a smoker without the variants, the researchers reported. And that same smoker on average lights up two extra cigarettes a day and has a much harder time quitting than smokers who don't have these genetic differences.
The researchers disagreed on whether the variants directly increased the risk of lung cancer or did so indirectly, by causing more smoking.
The three studies, funded by governments in the U.S. and Europe, are being published Thursday in the journals Nature and Nature Genetics.
The scientists studied the genes of more than 35,000 white people of European descent in Europe, Canada and the United States. Blacks and Asians will be studied soon and may yield different results, scientists said.
They aren't quite sure if what they found is a set of variations in one gene or in three closely connected genes.
The gene variations, which govern nicotine receptors on cells, could eventually help explain some of the mysteries of chain smoking, nicotine addiction and lung cancer. These oddities include why there are 90-year-old smokers who don't get cancer and people who light up an occasional cigarette and don't get hooked.
"This is really telling us that the vulnerability to smoking and how much you smoke is clearly biologically based," said psychiatry professor Dr. Laura Bierut of Washington University in St. Louis, a genetics and smoking expert who did not take part in the studies. She praised the research as "very intriguing."
The smoking rate among U.S. adults has dropped from 42 percent in 1965 to less than 21 percent now.
The new studies are surprising in that they point to areas of the genetic code that are not associated with pleasure and the rewards of addiction.
That may help explain why some people can quit and others fail, said Dr. Nora Volkow, director of the National Institute of Drug Abuse in Bethesda, Md., which funded one of the studies.
"It opens our eyes," Volkow said Wednesday. "Not everyone takes drugs for the same reason. Not everyone smokes cigarettes for the same reasons."
One clue is in the location of the just-discovered variants, on the long arm of chromosome 15, Volkow said. It is in an area that, when damaged during tests on animals, makes them depressed and anxious. While some people smoke because it helps them focus or gives them a physiological reward, others do it to stave off depression.
That suggests that adding antidepressants to some smokers' treatment could help them kick the habit.
Bierut said a simple, inexpensive test could be developed to screen people for the variants. Kari Stefansson, lead author of the largest of the three studies, agreed. He is chief executive of deCode Genetics of Iceland, which already does prostate cancer genetic tests.
Such testing could carry risks all its own, bioethicist Arthur Caplan of the University of Pennsylvania warned. People who have been found to have a genetic predisposition to addiction and lung cancer could find it harder to get health or life insurance, or their employer might drop their coverage, he said.
"The good news is that getting these risk estimates will help focus anti-smoking campaigns, and some people will want to voluntarily get into anti-addiction programs early, where they will probably work better," Caplan said in an e-mail. But if such testing is done, it should be voluntary, and the results should be kept private, he said.
Smoking-related diseases worldwide kill about one in 10 adults, according to the World Health Organization.
Among the findings:
— Smokers who get the set of variants from only one parent see a risk of lung cancer that is about one-third higher than that of people without the variants. They also smoke about one more cigarette a day on average than other smokers. This group makes up about 45 percent of the population studied.
— Smokers who inherit the variants from both parents have nearly a 1-in-4 chance of developing lung cancer. Their cancer risk is 70 to 80 percent higher than that of smokers without the genetic variants. They smoke on average two extra cigarettes a day. This group accounts for about one in nine people of European descent.
— Smokers who don't have the variants are still more than 10 times more likely to get lung cancer than nonsmokers. Smokers without the variant have about a 14 percent risk of getting lung cancer. The risk of lung cancer for people who have never smoked is less than 1 percent, said another study author, Paul Brennan of the International Agency for Research on Cancer in Lyon, France.
Brennan and Amos, working on different teams, linked the genetic variation itself — when triggered by smoking — directly to lung cancer. Brennan said the nicotine receptors that the variants act on also can stimulate tumor growth.
But Stefansson said the increased lung cancer risk was indirect — the variants led to more smoking, which led to more cancer.
For Stefansson, the research hits home. His father, a smoker, died of lung cancer. And Stefansson, who doesn't smoke, frequently lectures his 23-year-old daughter "who smokes like a chimney." She acts as if she is immortal and smoking can't kill her, Stefansson said. But his own research shows that her genes are probably stacked against her.
———
Subscribe to:
Posts (Atom)