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An Important Piece of the Puzzle: Why Some Smokers Get Lung Cancer and Others Don’t
Author
Dr Pennell

Admit it. You have probably wondered why you or your loved one was unlucky enough to get lung cancer while that obnoxious neighbor or coworker has smoked 2 packs a day for 50 years and doesn’t even have a cough. In fact, only about 15% of male smokers and 10% of female smokers eventually develop lung cancer. The field at large has been searching for why some smokers get lung cancer and others don’t for many years, and while progress has been made the answer has been elusive.

In an exciting development that may explain some of this disparity, just recently published in Cancer Research, investigators at the University of Minnesota led by Dr. Jian-Min Yuan have discovered that urinary levels of a certain carcinogen in tobacco smoke correlate strongly with lung cancer risk.

To back up for just a second, we have known for years that tobacco smoke contains many carcinogenic compounds, and that overall there is an association between how much and how long you smoke and your risk of lung cancer. What hasn’t been known is the relative contribution of each carcinogen to this risk (which ones are important and which are less so), or how the body’s ability to metabolize and eliminate these carcinogens helps or hurts.

Dr. Yuan focused on a group of compounds collectively called NNAL, which are a metabolic byproduct of the tobacco smoke carcinogen NNK. NNAL causes lung cancer in rats, but how important it is to human lung cancer is unknown. NNAL is easily measured in urine, so the investigators were able to measure the levels of NNAL in a group of patients who developed lung cancer and relate these levels to risk of developing lung cancer.

The patients were part of a large cohort of Chinese smokers (over 80,000) who had been followed over time for many years in order to learn about risks of smoking. About 350 cases of lung cancer were diagnosed in this group, and urine NNAL (collected at study inception, long before they developed cancer) was measured in 246 of them. Cotinine, a metabolite of tobacco smoke whose levels are proportional to the amount of tobacco smoked was also measured. Urine NNAL and cotinine were also measured in a matched group of people with comparable risk factors (smoking levels, age, gender, geography) in a process called a nested case-control study.

What they found was that higher levels of NNAL in the urine, regardless of how much the patients actually smoked, correlated with a higher risk of lung cancer. The average NNAL level in cancer patients was higher than in matched smokers with no lung cancer, and patients with the highest NNAL and cotinine levels had 8.5 times the risk of developing lung cancer of people who had the lowest urinary levels of NNAL!

In other words, some of the patients were almost 9 times more likely to get lung cancer than others smoking the same amount, based only on the level of NNAL and continine in the urine taken a single time, years before they developed cancer.

This has the potential, if verified and found to apply to people outside Asia, to provide an easy and non-invasive test of risk in smokers, and even in people exposed to second hand smoke who might be at higher risk of lung cancer than the smokers around them! You can imagine that if someone's NNAL levels are high, every attempt should be made to quit smoking.

Of course, some may use this data to suggest that it is safe to smoke if your NNAL levels are low, since the risk of lung cancer may be less. Don’t forget that more smokers die of heart attack and stroke than from lung cancer, so you aren’t out of the boat! Smoking is and always will be bad for you, but we may now be closer to learning just how bad.

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