Children exposed to secondhand tobacco smoke are at increased risk for lung cancer later in life -- even if they never smoke themselves, researchers said. That risk is also modulated by genetic variation in a gene involved in innate immunity, according to Curtis Harris, MD, of the National Cancer Institute in Bethesda, Md., and colleagues. The findings come from a study in the December issue of Cancer Epidemiology, Biomarkers & Prevention, which is dedicated to tobacco research. Harris and colleagues looked at the risk of lung cancer among participants in the National Cancer Institute-Maryland Lung Cancer study and also in an independent case-control study at the Mayo Clinic in Rochester, Minn.

Action Points  Explain to interested patients that these studies implicate secondhand smoke exposure in the development of cancer, even among people who themselves have never smoked.
Note that the research was limited because exposure data was based on personal recall and may have been subject to bias.
They had two hypotheses: that exposure to smoke in childhood would increase the risk of disease and that the risk would be modulated by variations in the gene for mannose binding lectin-2 (MBL).

Variations in the gene that result in high levels of the protein in the blood have been associated with respiratory problems, Harris and colleagues noted.

The Maryland study included 624 participants with lung cancer and 348 healthy controls. Their exposure to secondhand smoke was evaluated using in-person interviews, and investigators collected DNA samples in order to genotype the MBL2 gene.

In that study, the odds of lung cancer among people who had never smoked was more than doubled if they were exposed to smoke in childhood (OR 2.25, 95% CI 1.04 to 4.90)

At the same time, gene variations associated with high circulating levels of MBL and increased activity of the gene were linked to increased risk of cancer (OR 2.52, 95% CI 1.13 to 5.60).

Both findings were confirmed in the Mayo study, which enrolled 461 people who had never smoked, including 172 lung cancer patients and 289 controls. The lung cancer risks were as follows: Exposed to smoke in childhood (OR 1.47, 95% CI 1.00 to 2.15). MBL2 variation linked to high circulating levels of MBL and increased gene activity (OR 2.78, 95% CI 1.18 to 3.85).

The research is limited, the researchers wrote, by the difficulty of following a childhood cohort through adulthood in order to monitor cancer incidence. As a result, exposure data is based on personal recall and may be subject to bias.

On the other hand, they noted, the results were statistically significant, "suggesting a strong and genuine association in two independent cohorts that will need to be replicated in other studies."

In a separate report, investigators in California probed the effect of secondhand smoke on breast cancer among women who had never smoked.

Overall, there was no clear picture, according to Peggy Reynolds, PhD, of the Northern California Cancer Center in Berkeley, Calif., and colleagues.

Instead, risk seemed to be concentrated in postmenopausal women with a high adult exposure to secondhand smoke, Reynolds and colleagues wrote.

The researchers analyzed the prospective California Teachers Study, which collected detailed information on passive smoke exposure by setting and by age at exposure in 1997.

Participants were 57,523 women who had never smoked and had no history of breast cancer. In the following 10 years, 1,754 participants were diagnosed with invasive breast cancer, Reynolds and colleagues found.

Overall, more exposure to secondhand smoke led to nonsignificant increases in the risk of breast cancer, the researchers wrote.

However, for women exposed when they were 20 or older, the risk was elevated at the highest level of cumulative exposure (HR 1.18, 95% CI 1.00 to 1.40), the researchers reported.

The risk was highest primarily among postmenopausal women (HR 1.25, 95% CI 1.01 to 1.56), they found.

The breast cancer study had support from California's Tobacco Related Disease Research Program, the National Cancer Institute, and the California Breast Cancer Research Fund. The researchers reported no conflicts.

The lung cancer study had support from the NIH, the National Cancer Institute, and the Center for Cancer Research. The researchers reported no conflicts.

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Smokers who light up shortly after waking up have greater exposure to nicotine than those who wait until later in the day -- regardless of how many cigarettes they smoke, researchers found. Levels of cotinine, a nicotine metabolite, were higher in those who smoked 10 cigarettes a day and lit up within a half hour of waking up than in those who smoked 20 cigarettes a day but waited at least 30 minutes to have their first one (326 versus 268 ng/mL), according to Joshua Muscat, PhD, MPH, of Penn State College of Medicine in Hershey, Pa., and colleagues. "So in essence, it's almost as if [early smokers] are being exposed to twice the amount of cigarette smoke as people who refrain from smoking for a longer period after waking up," Muscat said in an interview. The findings were reported online in Cancer Epidemiology, Biomarkers & Prevention.Action Points  Explain to interested patients that smokers who lit up their first cigarette shortly after waking were exposed to more nicotine than those who waited a half hour or more -- regardless of how many cigarettes they smoked during the day.
Explain to interested patients that this study could not determine why cotinine levels were higher in smokers who had their first cigarette soon after waking up.

Muscat said that the reason early smokers had higher cotinine levels was unclear, but that he suspects it has to do with the intensity with which they smoke. More intense smoking involves taking more puffs per cigarette and inhaling more deeply.

This could have implications for the design of smoking-cessation interventions, he said.

"We may have to consider not only reducing the number of cigarettes they smoke but also trying to reduce the intensity of their smoking in order to effectively lower their biological levels of nicotine," he said.

In the study, Muscat and his colleagues explored factors related to cotinine levels in 252 black and white adult smokers in Westchester County, N.Y. All the participants smoked at least five cigarettes a day for at least one year.

Each smoker underwent the six-item Fagerström Test for Nicotine Dependence. One item asks individuals to report how long they wait after waking up to smoke their first cigarette.

Two groups -- high and low dependence -- emerged when the researchers began looking at the data.

Smokers in the low-dependence group waited more than 30 minutes before lighting their first cigarette. Nearly all smoked 20 or fewer cigarettes a day. Plasma cotinine levels were relatively low (mean 204 ng/mL).

Smokers in the high-dependence group lit up within a half hour of waking up, and the number of daily cigarettes varied widely from six to 70. Plasma cotinine levels were nearly double those in the low-dependence group (397 ng/mL).

Although cotinine levels increased linearly with the number of cigarettes smoked per day in the low-dependence group, there was no such relationship in the high-dependence group.

"The lack of a significant linear relationship between cigarette frequency and cotinine in the highly dependent group indicates important physiologic or metabolic factors such as the saturation of nicotine uptake and nicotine metabolism may be occurring," the researchers said.

After adjustment for the number of daily cigarettes and race, there was a significant inverse relationship between the time to first cigarette and plasma cotinine levels: 5 minutes or less: 437 ng/mL 6 to 30 minutes: 352 ng/mL 31 to 60 minutes: 229 ng/mL More than 60 minutes: 215 ng/mL

All of the differences were significant (P≤0.05), except for that between smoking 31 to 60 minutes after waking up and smoking more than an hour after waking up (P=0.85).

In the journal article, the researchers noted that variations in cotinine levels can be affected by various factors, including genetic variability in addiction, environmental factors, and unmeasured physiological and psychological characteristics of nicotine dependence.

In addition, they wrote, smoking intensity could be the result of factors beyond nicotine dependence, including the tar yield and taste of cigarettes.

The study was supported by grants from the National Cancer Institute and the U.S. Public Health Service.

The authors did not report any conflicts of interest.

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A low-calorie diet can reduce the symptoms of obstructive sleep apnea in obese patients and in some cases cure the condition, Swedish researchers said. In a randomized controlled trial, obese men who spent seven weeks on a very low-calorie liquid diet saw their sleep apnea drop from severe or moderate to mild or normal, according to Kari Johansson, a PhD candidate at the Karolinska Institute in Stockholm, and colleagues. At the same time, obese men in the control group -- who maintained their normal diet -- saw no change, Johansson and colleagues reported online in BMJ.

Action Points  Explain to interested patients that obesity is a major risk factor for obstructive sleep apnea.
Note that this randomized controlled trial showed that a low-energy diet can relieve the symptoms of the disease, at least over a short term.
Only one other randomized trial has looked at the effect of weight loss in sleep apnea, Johansson and colleagues wrote, and that study did not include men with moderate or severe disease.

To help fill the gap, the researchers enrolled 63 men with a body mass index between 30 and 40. They randomly assigned 30 men to follow a seven-week, 550-kcal liquid regimen (the Cambridge Diet), followed by a two-week period of gradual reintroduction of normal food.

The remaining 33 men formed a control group and continued their normal diet, although two dropped out when they found they were to be controls.

At the start of the study, the average apnea-hypopnea index (AHI) was 37 in both groups -- meaning they averaged 37 episodes of stopped or shallow breathing per hour of sleep.

An index of less than 5 is regarded as normal, while scores of 5 through 14, 15 through 29, and 30 or more indicate mild, moderate, or severe obstructive sleep apnea, respectively.

At the end of the nine weeks, the researchers reported: Men on the diet lost an average of 41 pounds, while those in the control group gained an average of 2.4 pounds. On average, the dieting men lost 5.7 points on their BMI, compared with a gain of 0.3 points in the control group. Twenty-two of the 30 dieters were no longer obese, while all of the control participants remained obese. The average AHI among the dieters was 12 (mild), compared with 35 (severe) in the control group. Five of the dieters were disease-free, with an AHI of less than 5, and half had mild disease. Only one participant in the control group was below 15 on the AHI. Researchers identified eight transient adverse effects that might have been caused by the diet, including three cases of constipation and two of elevated alanine aminotransferase concentrations. There were no adverse events in the control group.

The main limitation of the study, Johansson and colleagues wrote, is that its short length made the long-term effect difficult to determine.

Even so, the study fills a "major gap" in evidence-based treatment of sleep apnea, according to Nathaniel Marshall, PhD, of the University of Sydney, and Ronald Grunstein, MD, PhD, of the Royal Prince Alfred Hospital, both in Sydney, Australia.

Writing an accompanying editorial, Marshall and Grunstein noted that much sleep apnea research has focused on mechanical interventions, such as continuous positive airway pressure machines.

The Swedish study provides "the first high-quality evidence that moderate-severe obstructive sleep apnea can be treated with weight loss," they wrote in the journal.

But they also noted that the study was only nine weeks long, "which leaves open the question of the long-term sustainability of the weight loss."

The study had support from Cambridge Manufacturing Company Limited and Novo Nordisk Scandinavia AB. The researchers declared no competing interests.

Marshall and Grunstein did not report any competing interests

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