Smoking Causes Genetic Damage Within Minutes After Inhaling

In research described as "a stark warning" to those tempted to start smoking, scientists are reporting that cigarette smoke begins to cause genetic damage within minutes -- not years -- after inhalation into the lungs.

Their report, the first human study to detail the way certain substances in tobacco cause DNA damage linked to cancer, appears in Chemical Research in Toxicology, one of 38 peer-reviewed scientific journals published by the American Chemical Society.

Stephen S. Hecht, Ph.D., and colleagues point out in the report that lung cancer claims a global toll of 3,000 lives each day, largely as a result of cigarette smoking. Smoking also is linked to at least 18 other types of cancer. Evidence indicates that harmful substances in tobacco smoke termed polycyclic aromatic hydrocarbons, or PAHs, are one of the culprits in causing lung cancer. Until now, however, scientists had not detailed the specific way in which the PAHs in cigarette smoke cause DNA damage in humans.

The scientists added a labeled PAH, phenanthrene, to cigarettes and tracked its fate in 12 volunteers who smoked the cigarettes. They found that phenanthrene quickly forms a toxic substance in the blood known to trash DNA, causing mutations that can cause cancer. The smokers developed maximum levels of the substance in a time frame that surprised even the researchers: Just 15-30 minutes after the volunteers finished smoking. Researchers said the effect is so fast that it's equivalent to injecting the substance directly into the bloodstream.

"This study is unique," writes Hecht, an internationally recognized expert on cancer-causing substances found in cigarette smoke and smokeless tobacco. "It is the first to investigate human metabolism of a PAH specifically delivered by inhalation in cigarette smoke, without interference by other sources of exposure such as air pollution or the diet. The results reported here should serve as a stark warning to those who are considering starting to smoke cigarettes," the article notes.

When good cholesterol is even better

HDL's efficiency, not just quantity, appears important for heart health

By Tina Hesman Saey

How much good cholesterol a person has is not as important as how well that good cholesterol works to stop heart disease, a new study suggests.
High-density lipoprotein — also known as HDL, or “good” cholesterol — is healthy for the heart, previous studies have indicated. People with high blood levels of the molecule tend to have lower risk of developing heart disease than people with low levels. But a new study suggests that the amount of good cholesterol in the blood may not be the most important factor in protecting against clogged arteries and cardiovascular disease. The study, published January 13 in the New England Journal of Medicine, shows that HDL’s efficiency at removing fats from arteries is a better predictor of who will develop heart disease than is the level of good cholesterol in the blood.
The results “suggest that just measuring HDL levels isn’t enough to figure out what’s going on,” says Jay Heinecke, an endocrinologist at the University of Washington in Seattle, who wrote an editorial comment on the research in the same issue of the journal. “It opens up the idea that there’s a lot we don’t know about HDL.”

In the study, some people’s good cholesterol was more efficient at relieving the white blood cells of a cholesterol burden than other people’s, found researchers led by Daniel Rader at the University of Pennsylvania School of Medicine in Philadelphia. Healthy people with this trait, known technically as a higher cholesterol efflux capacity, had less thickening of their carotid arteries than did people with less efficient cholesterol-clearing HDL. And, in a separate group of people, HDL functioning was a better indicator than HDL levels of whether the person had heart disease, the team found.

Doctors won’t be able to test their patients’ HDL efficiency any time soon. “We don’t yet have an assay or a test that can be used in a clinical setting,” says Rader. But the work does shed light on some important questions about how good cholesterol works.

“It says that the good cholesterol is more complicated than the bad cholesterol story,” says Christopher Cannon, a cardiologist at Brigham and Women’s Hospital in Boston. Bad cholesterol can build up in arteries, thickening the vessels and narrowing the space blood can squeeze through, so reducing artery damage is as straightforward as lowering the amount of bad cholesterol in the blood. “But good cholesterol actually has to do something to pull bad cholesterol out of the arteries” and send it to the liver for disposal, Cannon says. Exactly how the molecule accomplishes that task efficiently remains to be seen, and is next on the list for Rader and his colleagues to study.

“Now they have to put themselves to work,” says Valentin Fuster, director of the Mount Sinai Heart center in New York City, ticking off a list of research questions raised by the finding. Measurements of thickening of the carotid artery, which feeds oxygen-rich blood to the head and neck, aren’t good indicators of what is happening to arteries feeding the heart, he notes. While the study has value, Fuster would like to see more work showing how HDL efficiency affects arterial disease and how cholesterol-clearing capacity relates to other heart disease risk factors, such as age.

Gene breakthrough in diabetes study

Scientists have identified a gene which plays a role in how a commonly used diabetes drug works - creating a new area for drug development in the future.

Metformin is a drug taken by millions of people with diabetes across the globe and has been in use for more than 50 years.

It has been shown to protect against heart disease and eye and kidney disease in people with Type 2 diabetes and has also been shown to have benefits against cancer. But scientists have not known exactly how metformin works.

New research carried out at the University of Dundee, Oxford University and the Wellcome Trust Sanger Institute as part of the Wellcome Trust Case Control Consortium shed light on how the body works with and makes use of metformin.

Dr Ewan Pearson, Professor Colin Palmer and colleagues based in the Biomedical Research Institute at the University of Dundee used data from a clinical information system of patients with diabetes linked to donated blood samples from 20,000 people in the Tayside area of Scotland in the research.

They were able to determine how well metformin worked in 2,800 people and identified an area of chromosome 11, which includes a gene called ATM (Ataxia Telangiectasia Mutated), that altered how well people responded to metformin.

ATM is a gene that is known to be involved in the DNA damage response system of cells, a mechanism that if faulty can lead to the development of cancer, Dr Pearson said.

"We were expecting to find genes involved in blood sugar regulation so the finding that ATM is involved in metformin response was totally unexpected. Although ATM has been widely studied by cancer scientists, no one previously thought it had a role in how this commonly used diabetes drug worked."

Prof Palmer said: "This is an important development in defining how individuals may respond differently to diabetes drugs, but further work is required before we have enough information to be able to reliably use genetic testing in the clinic to guide treatment of common forms of Type 2 diabetes."

The research was funded by the Wellcome Trust and Diabetes UK and is published in the journal Nature Genetics. Diabetes UK has now awarded Dr Pearson further funding to continue his research using new genetic techniques on 8,000 people with Type 2 diabetes.

Study finds evidence of increased lung cancer risk among tuberculosis patients

Although a clear association of tuberculosis with lung cancer remains to be established, a new study published in the January issue of theJournal of Thoracic Oncology provides compelling evidence of increased lung cancer risk among people with tuberculosis.

Researchers at China Medical University and Hospital in Taiwan randomly selected 1 million patients covered under the country’s National Health Insurance (NHI) program. All patients aged 20 years and older with a new diagnosis of tuberculosis between 1998 and 2000 were identified as the exposed cohort and all people without tuberculosis history were the non-exposed cohort. Patients with any cancer diagnosis were excluded to ensure that all participants were cancer-free at the start of both cohorts. Overall, 716,872 adults were eligible for the analysis – 4,480 in the tuberculosis cohort and 712,392 in the non-tuberculosis cohort.

Both groups were followed from 2001 through 2007. Results showed that patients with tuberculosis were 10.9 times more likely than non-tuberculosis patients to develop lung cancer (26.3 versus 2.41 per 10,000 person-years). Mortality was also much higher in the patients with tuberculosis than in the non-tuberculosis patients (51.1 versus 8.2 per 10,000 person-years).

“Tuberculosis is a very common chronic disease worldwide; people in the developing and undeveloped areas suffer with it mostly,” said Dr. Chih-Yi Chen, one of the researchers. “It is well known that lung cancer is causally associated with smoking. Less attention has been focused on whether people with tuberculosis are also at higher risk of developing lung cancer. With the universal health insurance claims data of Taiwan, we identified 4,480 patients with tuberculosis from a group of 716,872 people and followed them for eight years or longer. The incidence of lung cancer in these tuberculosis patients was 11 times greater than people without tuberculosis. The risk of lung cancer may increase further to almost 16 times greater if patients with tuberculosis also suffer from chronic obstructive pulmonary disease. This study suggests that it is also important to watch out for lung cancer prevention in the campaign against tuberculosis.”

The research was supported by the National Science Council, Executive Yuan, Taiwan; the Department of Health Clinical Trial and Research Center of Excellence; China Medical University Hospital; and Taiwan Department of Health, China Medical University Hospital Cancer Research of Excellence.

About the Journal of Thoracic Oncology:

The Journal of Thoracic Oncology (JTO) is the official monthly journal of the International Association for the Study of Lung Cancer (IASLC). It is a prized resource for medical specialists and scientists who focus on the detection, prevention, diagnosis and treatment of lung cancer. It emphasizes a multidisciplinary approach, including original research (clinical trials and translational or basic research), reviews and opinion pieces.

To find out more about the JTO please visit journals.lww.com. To learn more about the IASLC please visit iaslc.org.