BOSTON — The widely held belief that e-cigarettes do not pose a cancer threat may be wishful thinking, according to the results of a new pilot study that focuses on their potential impact on bladder cancer.

The small study showed that two known carcinogens, otoluidine and 2-naphthylamine, were found in the urine of e-cigarette users but not in nonusers.

"That's concerning because we know there are people who genetically susceptible to developing bladder cancer," said lead study author, Thomas Fuller, MD, a urologist at the University of Pittsburgh in Pennsylvania.

Traditional cigarette smoking is a major risk factor for bladder cancer. e-Cigarettes have gained popularity, in part because they are perceived as a safer alternative, he explained.

"No level of exposure to these carcinogens is without risk," Dr Fuller told Medscape Medical News after he discussed the study at press conference today at the American Urological Association (AUA) 2017 Annual Meeting. However, he also admitted that the clinical implication of the findings about otoluidine and 2-naphthylamine is unknown.

Previous studies of traditional cigarette smokers have identified otoluidine and 2-naphthylamine as the two most carcinogenic molecules for the bladder, Dr Fuller said.

In the new study, 12 of the 13 e-cigarette users whose urine was analyzed had both otoluidine and 2-naphthylamine detected (limits of detection were 100 ng/mL and 10 ng/mL, respectively). None of the 10 controls were positive for the compounds.

Specifically, among e-cigarette users, there were 2.3-fold mean concentration level increases for otoluidine (P = .0013) and a 1.3-fold increase for 2-naphthylamine (P = .014) compared with controls.

Notably, all study participants, when interviewed by investigators, said that e-cigarettes were "safe."

Dr Fuller also commented that, among traditional cigarette smokers, the urine levels of these molecules would be "greater."

The investigators examined study participants' urine for three other carcinogens — benz(a)anthracene, benzo(a)pyrene, and 1- hydroxypyrene — but found no significant findings for these molecules.

The study's e-cigarettes users were also ex-smokers of traditional cigarettes; they had a median of 20 years of use. Importantly, they had quit traditional cigarettes for a median of 15 months before the current study. And they had been using e-cigarettes for a median of 26 months. So, there was a period in the past in which most participants overlapped use of both forms of smoking.

Press conference moderator, Sam Chang, MD, a urologist from Vanderbilt University in Nashville, Tennessee, wondered whether there was a correlation between frequency of e-cigarette use and urine levels of the carcinogens.

Dr Fuller revealed that they could not assess that because most of the study participants (84.6%) used e-cigarettes more than 28 times a week (about four times a day). The study questionnaire had assumed that this four-times-a-day frequency would be the upper limit of use. But it turned out to be a lower limit. "We underestimated how often people are using these e-cigarettes," he said.

Bladder Cancer Research Is Just Starting

Dr Chang believes the study, despite its small size, is an important step in understanding e-cigarettes and their potential bladder cancer threat.

The new study reveals that problematic chemical molecules are "processed, end up in the urine, which end up sitting in the bladder, which inevitably will have some impact on the likelihood of the development of cancer," he said.

Dr Chang also repeated the importance of a slide shown by Dr Fuller depicting the skyrocketing e-cigarette use among middle school and high school students from 2013 to 2015, with a jump in users from about 8% to 25% of all students over that time.

As a father of three school-aged daughters, Dr Chang said the threat of e-cigarette use in their age groups is "scary, scary."

Dr Fuller acknowledged that research into e-cigarettes and their effect on the bladder lags behind research into their effect on the lungs.

"Maybe as a community, we [urologists] bought into the idea that this was going to be a much safer alternative because there is no combustion," he said.

Dr Fuller said that a next step for research is that the new results need confirmation in a larger study. And more carcinogens must be examined. The current study looked at only five molecules that are considered carcinogenic.

The new results conflict somewhat with the message from other recent research from the United Kingdom that suggests e-cigarettes are largely safe and certainly an improvement over traditional cigarettes.

As reported by Medscape Medical News, former smokers who only used e-cigarettes or nicotine replacement therapy were substantially less likely to be exposed to carcinogens and toxins than those who continue to smoke, according to a cross-sectional study that looked at urine and blood samples.

Dr Fuller and Dr Chang have disclosed no relevant financial relationships.

American Urological Association (AUA) 2017 Annual Meeting. Abstract MP88-14. Presented May 15, 2017.

Follow Medscape senior journalist Nick Mulcahy on Twitter: @MulcahyNick

For more from Medscape Oncology, follow us on Twitter: @MedscapeOnc </s> Attention smokers: For every year that you continue your pack-a-day habit, the DNA in every cell in your lungs acquires about 150 new mutations.

Some of those mutations may be harmless, but the more there are, the greater the risk that one or more of them will wind up causing cancer.

The threat doesn’t stop there, according to a study in Friday’s edition of the journal Science. After a year of smoking a pack of cigarettes each day, the cells in the larynx pick up roughly 97 new mutations, those in the pharynx accumulate 39 new mutations, and cells in the oral cavity gain 23 new mutations.

Even organs with no direct exposure to tobacco smoke appear to be affected. The researchers counted about 18 new mutations in every bladder cell and six new mutations in every liver cell for each “pack-year” that smokers smoked.

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The findings are based on a genetic analysis of 5,243 cancers, including 2,490 from smokers and 1,063 from patients who said they had never smoked tobacco cigarettes.

At this point, it should come as no surprise that cigarettes are bad for your health. The U.S. surgeon general has warned about the dangers of smoking for more than 50 years. The American Cancer Society recently calculated that in a single year, at least 167,133 cancer deaths in the U.S. could be blamed on smoking.

But the new study offers a clearer picture of how smoking does its deadly damage.

The researchers used powerful supercomputers to compare thousands of cancer genome sequences. The computers grouped the sequences into about 20 distinct categories, or “mutational signatures.” Mutations tied to five of these signatures were more common in tumors from smokers than in tumors from nonsmokers.

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One of the signatures involves a specific DNA nucleobase change — instead of a C for cytosine, there was an A for adenine — that “is very similar” to the change that occurs in the lab when cells are exposed to benzo[a]pyrene, a compound that the International Agency for Research on Cancer says is carcinogenic to humans.

Most of the lung and larynx cancers obtained from smokers had this type of mutation, the researchers reported. They also found that the signature was more common among smokers than nonsmokers.

Another mutational signature was characterized by Cs that should have been Ts (thymine) and vice versa. Although these changes can be found in all kinds of cancers, the signature was 1.3 to 5.1 times more common in tumors from smokers than in tumors from nonsmokers, according to the study.

The researchers said they think these kinds of mutations have the effect of speeding up the “clock” inside of cells. The faster a cellular clock runs, the more chances the cell’s DNA has to mutate.

“The way tobacco smoking causes cancer is more complex than we thought,” study coauthor Mike Stratton, director of the Wellcome Trust Sanger Institute in England, said in a statement.

karen.kaplan@latimes.com

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WASHINGTON — Smoking a pack of cigarettes a day causes an average of 150 mutations a year in lung cells, according to a new study that identifies specific ways smoke exposure damages DNA.

The research, published on Thursday in the journal Science, analyses and compares tumours, providing the first accurate measure of the devastating genetic damage smoking inflicts not only in lungs but also in other organs not directly exposed to smoke.

Although it was previously known that smoking contributes to at least 17 types of human cancers, it had remained unclear exactly how cigarettes caused tumours, according to the researchers from Britain's Wellcome Trust Sanger Institute and the Los Alamos National Laboratory in the United States.

Although they saw the largest number of genetic mutations in lung tissue, other parts of the body also displayed changes in DNA, helping explain how smoking causes various types of cancer.

Cigarettes contain more than 7,000 different chemicals, of which 70 are known to be carcinogenic, the researchers said, pointing to the complexity of how smoke interacts with the body.

"This study offers fresh insights into how tobacco smoke causes cancer," said Ludmil Alexandrov of the Los Alamos National Laboratory, one of the study's main co-authors.

"Before now, we had a large body of epidemiological evidence linking smoking with cancer, but now we can actually observe and quantify the molecular changes in the DNA due to cigarette smoking," he added.

"With this study, we have found that people who smoke a pack a day develop an average of 150 extra mutations in their lungs every year, which explains why smokers have such a higher risk of developing lung cancer."

In the first comprehensive analysis of the DNA of cancers linked to smoking, the scientists studied more than 5,000 tumors, comparing smokers' cancers with those of people who had never smoked.

They found specific molecular features of damage in the smokers' DNA, determined by the number of those mutations in different tumours.

Although the number of mutations within cancer cells varies between people, the new study identifies the additional "mutational load" tobacco smoking causes.

In other affected organs, the study shows smoking a pack a day causes an estimated average of 97 mutations in each cell of the larynx; 39 in the pharynx; 23 in the mouth; 18 in the bladder; and six mutations in every cell of the liver each year.

The research shows at least five distinct ways smoking damages DNA, the most common of which is found in most types of cancer: accelerating the speed of a cellular clock that appears to mutate DNA prematurely.

"Our research indicates that the way tobacco smoking causes cancer is more complex than we thought," Mike Stratton of Wellcome Trust Sanger Institute said.

"Indeed, we do not fully understand the underlying causes of many types of cancer," he added, pointing to other known causes, such as obesity.

But the new study of smoking-related cancers can help scientists better understand how all cancers develop and, possibly, how they can be prevented, Stratton said.

"The genome of every cancer provides a kind of 'archaeological record, in the DNA code, reflecting the exposure that causes mutations,” he added.

Smoking — the largest preventable cause of death — is responsible for at least six million deaths a year worldwide.

If current trends continue, the World Health Organisation says, smoking will kill more than a billion people in the 21st century. </s> (CNN) The vast amount of damage that smoking can have on your DNA has been revealed in a new study exploring how tobacco smoke affects cells within the human body.

Consuming a pack of cigarettes every day for a year can cause multiple changes in cells within various parts of the body, according to the study, published in the journal Science on Thursday.

The cells in parts of the body that are directly exposed to smoke are particularly damaged, with 150 mutations found to occur in lung cells within one year, 97 in the larynx and 39 in the oral cavity.

"Tobacco smoking damages DNA in organs directly exposed to smoke as well as speeds up a mutational cellular clock in organs that are both directly and indirectly exposed to smoke." said Ludmil Alexandrov of the Los Alamos National Laboratory in Los Alamos, New Mexico, who led the study.

In other words, it accelerates the occurrence of genetic mutations, increasing the risk of cancer.

"Before now, we had a large body of epidemiological evidence linking smoking with cancer, but now we can actually observe and quantify the molecular changes in the DNA due to cigarette smoking," Alexandrov said.

Tobacco smoke is a mixture of chemicals, of which 60 are known to be carcinogens thought to cause cancer by aiding the occurrence of mutations within genes. With an increased number of mutations, there's a greater chance that they will happen within known cancer-causing genes.

"With this study, we have found that people who smoke a pack a day develop an average of 150 extra mutations in their lungs every year, which explains why smokers have such a higher risk of developing lung cancer," Alexandrov said.

According to the American Lung Association, men who smoke are 23 times more likely to develop lung cancer than someone who's never smoked, and women are 13 times more likely.

The researchers scanned the genome sequences of more than 5,000 tumors from 17 types of cancer for which smoking is a risk factor. These were obtained from smokers and nonsmokers alike for comparison.

In addition to the mutations, the analysis found a range of "molecular signatures" -- patterns that are significantly different from other sequences in the DNA -- based on changes to DNA that were linked to people smoking.

One signature was found in tissues directly exposed to smoke, and an unrecognized signature was more widely found in all smoking-related cancers. That mysterious signature appeared to increase the rate of premature mutations and appeared to correlate with age, with the total number of mutations linking to the age when someone was diagnosed.

"Mutations caused by direct DNA damage from carcinogens in tobacco were seen mainly in organs that come into direct contact with inhaled smoke," he added. "In contrast, other cells of the body suffered only indirect damage, as tobacco smoking seems to affect key mechanisms in these cells that in turn mutate DNA."

The researchers also looked at any changes in DNA methylation -- the process in which a molecule known as a methyl group sits on the surface of DNA to influence gene activity -- and saw limited differences between smokers and nonsmokers.

"I think one of the interesting things in this paper is the lack of methylation changes in tumor DNA related to smoking, when we do see significant changes in normal DNA between smokers and nonsmokers," said Dr. James Flanagan, a cancer geneticist at Imperial College London who was not involved in the study.

Flanagan's recent research has found that tobacco leaves a legacy on a smoker's DNA through methylation to influence whether genes are active or silent. He believes it's presumptive to say there's no role for methylation in these changes.

"I would assume that means the methylation is just so much more variable in tumors that the smoking-associated markers get lost in the statistical analysis. You can't argue from this that methylation changes from smoking are not important for cancer development."

But these new findings still shed valuable light on the way tobacco smoke increases the risk of cancer, particularly in parts of the body that are not actually exposed to smoke.

"The genome of every cancer provides a kind of 'archaeological record,' written in the DNA code itself, of the exposures that caused the mutations that lead to the cancer," said Sir Mike Stratton, director of the Wellcome Trust Sanger Institute in the UK, who co-led the research, in a statement. "Our research indicates that the way tobacco smoking causes cancer is more complex than we thought."

Stratton added, "this study of smoking tells us that looking in the DNA of cancers can provide provocative new clues to how cancers develop and thus, potentially, how they can be prevented." </s> WASHINGTON -- Smoking a pack of cigarettes a day causes an average of 150 mutations a year in lung cells, according to a new study that identifies specific ways smoke exposure damages DNA.

The research, published Thursday in the journal Science, analyzes and compares tumors, providing the first accurate measure of the devastating genetic damage smoking inflicts not only in lungs but also in other organs not directly exposed to smoke.

Although it was previously known that smoking contributes to at least 17 types of human cancers, it had remained unclear exactly how cigarettes caused tumors, according to the researchers from Britain's Wellcome Trust Sanger Institute and the Los Alamos National Laboratory in the United States.

Although they saw the largest number of genetic mutations in lung tissue, other parts of the body also displayed changes in DNA, helping explain how smoking causes various types of cancer.

Cigarettes contain more than 7,000 different chemicals, of which 70 are known to be carcinogenic, the researchers said, pointing to the complexity of how smoke interacts with the body.

"This study offers fresh insights into how tobacco smoke causes cancer," said Ludmil Alexandrov of the Los Alamos National Laboratory, one of the study's main co-authors.

"Before now, we had a large body of epidemiological evidence linking smoking with cancer, but now we can actually observe and quantify the molecular changes in the DNA due to cigarette smoking," he added.

"With this study, we have found that people who smoke a pack a day develop an average of 150 extra mutations in their lungs every year, which explains why smokers have such a higher risk of developing lung cancer." </s> The findings come from a study of the devastating genetic damage, or mutations, caused by smoking in various organs in the body.

Publishing in the journal Science on Thursday, the researchers said the findings show a direct link between the number of cigarettes smoked in a lifetime and the number of mutations in the DNA of cancerous tumors.

The highest mutation rates were seen in lung cancers, but tumors in other parts of the body - including the bladder, liver and throat - also had smoking-associated mutations, they said. This explains why smoking also causes many other types of cancer beside lung cancer.

Smoking kills six million people a year worldwide and, if current trends continue, the World Health Organization predicts more than 1 billion tobacco-related deaths this century.

Cancer is caused by mutations in the DNA of a cell. Smoking has been linked with at least 17 types of cancer, but until now scientists were not clear on the mechanisms behind many of them.

Ludmil Alexandrov of Los Alamos National Laboratory in the United States, one of those who carried out the research, explained that in particular, it had until now been difficult to explain how smoking increases the risk of cancer in parts of the body that don't come into direct contact with smoke.

"Before now, we had a large body of epidemiological evidence linking smoking with cancer, but now we can actually observe and quantify the molecular changes in the DNA," he said.

This study analyzed over 5,000 tumors, comparing cancers from smokers with those from people who had never smoked.

It found certain molecular fingerprints of DNA damage – called mutational signatures – in the smokers' DNA, and the scientists counted how many of these were in different tumors.

In lung cells, they found that on average, smoking a pack of cigarettes a day led to 150 mutations in each cell every year. Each mutation is a potential start point for a "cascade of genetic damage" that can eventually lead to cancer, they said.

The results also showed that a smoking a pack of cigarettes a day led to an average 97 mutations in each cell in the larynx, 39 mutations for the pharynx, 23 for the mouth, 18 for the bladder, and six mutations in every cell of the liver each year.

Mike Stratton, who co-led the work at Britain's Wellcome Trust Sanger Institute, said it was a bit like digging in to the archaeology of each tumor

"The genome of every cancer provides a kind of archaeological record, written in the DNA code itself, of the exposures that caused the mutations," he said. "Looking in the DNA of cancers can provide provocative new clues to how (they) develop and thus, potentially, how they can be prevented." </s> A new study has observed detrimental changes in the mammary glands of female mice following exposure to chemicals used in unconventional oil and natural gas (UOG) extraction methods, which include fracking.

This could translate into important health implications for millions of people living in proximity to extraction sites and exposed to these chemicals through the water supply.

Fracking, or hydraulic fracturing, is a process by which several million litres of water mixed with a cocktail of chemicals is injected under high pressure into fossil fuel beds in order to increase output. Waste water from these operations can be heavily laced with radioactive compounds, heavy metals and the input chemicals, and is regarded by many as a potential major health risk.

The study in the journal Endocrinology was led by Laura Vandenberg, an environmental health researcher at the University of Massachusetts Amherst, USA.

She worked with gynaecologist Susan Nagel from the University of Missouri, who has previously researched the substances used in, and produced by, UOG methods and established that several were endocrine-disrupters capable of stunting development and suppressing reproductive hormones in mice.

Nagel and colleagues also found elevated levels of the same chemicals in ground and surface water sampled from major drilling sites in Colorado. They tested these on human cell cultures and demonstrated similar disturbances in reproductive hormone levels and their receptors.

The current study went one step further and looked at the effects of 23 chemicals used in the UOG process – including polycyclic aromatic hydrocarbons, alkenes, and volatile organics. The chemicals were administered in combination to pregnant mice in one of four doses. Other mice were exposed to an inert substance, to serve as controls.

The two lower doses were akin to concentrations measured in drinking water obtained from drilling regions, whereas the higher doses were comparable to concentrations found in industrial effluents. All, thus, represented environmentally significant levels for humans.

Mammary glands of the female offspring were studied at 21 days after birth, equating to pre-puberty, and at 85 days, equating to early adulthood.

No overt adverse effects were observed in the pre-pubescent pups. However, at 85 days, Vandenberg and colleagues detected mammary structures called terminal end buds, normally present only at puberty. Examining the buds at tissue level, they found abnormal multiple layers of epithelial cells, and excessive growth of the cells lining the ducts, indicative of pre-cancerous lesions.

The severity of the abnormal tissue correlated with the level of exposure to the chemicals the mice had received while still in the womb.

The authors are currently engaged in designing new studies to learn more about the long-term impacts that the 23-chemical concoction may have on mammary tumour development, progression and general gland function.

Vandenberg and her team are hopeful that their findings will prompt further studies into the health effects of UOG chemicals. </s> People who used e-cigarettes were more likely to kick the habit than those who didn’t, a new study found.

Nicotine patches, gums and medications are known to aid smoking cessation, but there’s no consensus on whether vaping devices can help anti-smoking efforts. The U.S. research is the largest look yet at electronic cigarette users and it found e-cigarettes played a role in helping people quit.

“It’s absolutely clear that e-cigarettes help smokers replace cigarettes,” said Peter Hajek, director of the health and lifestyle research unit at Queen Mary University in London, who wasn’t part of the study.

Smoking rates have been generally declining for decades. Health experts have credited taxes on tobacco products and anti-smoking ads for the drop.

E-cigarettes have been sold in the U.S. since 2007. Most devices heat a liquid nicotine solution into vapor and were promoted to smokers as a less dangerous alternative since they don’t contain all the chemicals, tar or odor of regular cigarettes.

Researchers analyzed and compared data collected by the U.S. Census from 2001 to 2015, including the number of adult e-cigarette users from the most recent survey.

About two-thirds of e-cigarette users tried to quit smoking compared to 40 percent of nonusers, the study found. E-cigarette users were more likely to succeed in quitting for at least three months than nonusers – 8 percent versus 5 percent.

The research was published online Wednesday in the journal, BMJ. It was funded by the National Institutes of Health.

The rate of people quitting smoking in the U.S. has remained steady at about 4.5 percent for years. It jumped to 5.6 percent in 2014-2015, representing about 350,000 fewer smokers. It was the first recorded rise in the smoking cessation rate in 15 years.

While national anti-smoking campaigns likely helped, the results show e-cigarette use also played an important role, said lead author Shu-Hong Zhu of the University of California, San Diego.

Hajek, who wasn’t part of the research, said vaping devices shouldn’t be strictly regulated, but instead be allowed to compete directly with cigarettes. “That way, smokers can get what they want without killing themselves,” he said.

Earlier this month, a House panel renewed its efforts to prevent the Food and Drug Administration from requiring retroactive safety reviews of e-cigarettes already on the market. </s> NEW YORK (AP) – People who used e-cigarettes were more likely to kick the habit than those who didn’t, a new study found.

Nicotine patches, gums and medications are known to aid smoking cessation, but there’s no consensus on whether vaping devices can help anti-smoking efforts. The U.S. research is the largest look yet at electronic cigarette users and it found e-cigarettes played a role in helping people quit.

“It’s absolutely clear that e-cigarettes help smokers replace cigarettes,” said Peter Hajek, director of the health and lifestyle research unit at Queen Mary University in London, who wasn’t part of the study.

Smoking rates have been generally declining for decades. Health experts have credited taxes on tobacco products and anti-smoking ads for the drop.

E-cigarettes have been sold in the U.S. since 2007. Most devices heat a liquid nicotine solution into vapor and were promoted to smokers as a less dangerous alternative since they don’t contain all the chemicals, tar or odor of regular cigarettes.

Researchers analyzed and compared data collected by the U.S. Census from 2001 to 2015, including the number of adult e-cigarette users from the most recent survey.

About two-thirds of e-cigarette users tried to quit smoking compared to 40 percent of non-users, the study found. E-cigarette users were more likely to succeed in quitting for at least three months than non-users — 8 percent versus 5 percent.

The research was published online Wednesday in the journal, BMJ. It was funded by the National Institutes of Health.

The rate of people quitting smoking in the U.S. has remained steady at about 4.5 percent for years. It jumped to 5.6 percent in 2014-2015, representing about 350,000 fewer smokers. It was the first recorded rise in the smoking cessation rate in 15 years.

While national anti-smoking campaigns likely helped, the results show e-cigarette use also played an important role, said lead author Shu-Hong Zhu of the University of California, San Diego.

Hajek, who wasn’t part of the research, said vaping devices shouldn’t be strictly regulated, but instead be allowed to compete directly with cigarettes. “That way, smokers can get what they want without killing themselves,” he said.

Earlier this month, a House panel renewed its efforts to prevent the Food and Drug Administration from requiring retroactive safety reviews of e-cigarettes already on the market.

Others warned that the long-term side effects of e-cigarettes are unknown.

“We just don’t know if moving to e-cigarettes is good enough to reduce the harm,” said Aruni Bhatnagar, director of the American Heart Association’s Tobacco Research and Addiction Center.

Chris Bullen, who authored an accompanying editorial , said although the long-term safety of e-cigarettes is unclear, any ill effects are “likely to be rare compared with the harms of continuing to smoke.”

The latest results strongly suggest that more lenient control of e-cigarettes could improve population health, said Bullen, a professor of public health at the University of Auckland.

“If every smoker was to change over to e-cigarettes completely, there would be a dramatic and almost immediate public health benefit,” he said in an email.
A small study shows that two known carcinogens, o-toluidine and 2-naphthylamine, were found in greater amounts in the urine of e-cigarette users than in nonusers. Previous studies of traditional cigarette smokers have identified o-toluidine and 2-naphthylamine as the two most carcinogenic molecules for the bladder.