Tuesday, May 13, 2008 | 6:16 p.m.

Lifelong Health by Dr. David Lipschitz

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Dr. David Lipschitz

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Variant Gene Increases Risk of Cancer in Smokers

More often than not, cigarette smoking leads to a long list of health problems. From cancer to heart failure, the effects of long-term smoking can arise in nearly every function of your body. And yet every once in a while, I see a patient who, at 85, has smoked for decades and gotten off virtually scot-free.

For those rare healthy smokers, we typically pass off their unlikely healthfulness to mere luck — until now. A series of articles recently published in Nature Genetics sheds light on this very situation; it's all in the genes.

Researchers sought to determine why some individuals who smoke are at greater risk of developing lung cancer than others. Two studies showed that a variation in a gene located on chromosome 15 (of the 23 pairs of chromosomes in each cell) increases the risk of lung cancer 30 percent in individuals who smoke.

When it comes to biology, we inherit one gene from each parent. So if you are unfortunate enough to inherit this gene from your mother and your father, smoking increases your risk of developing lung cancer by 70 percent.

The gene on chromosome 15 not only increases lung cancer risk but also dramatically increases the chance of becoming addicted to nicotine. A lead author of one of the studies, Dr. Paul Brenner, initially believed that the gene variation led to addiction. As a result, more cigarettes were smoked every day, causing a higher exposure to carcinogens in the cigarette smoke and hence a higher risk of lung cancer.

Further studies of this gene indicate that it actually changes the way in which nicotine binds to cells throughout the body. Altered nicotine binding to the brain may change the number of cigarettes required to achieve the necessary "buzz" from nicotine, therefore forcing the individual to smoke more. However, these studies clearly showed that variation of these genes also made lung cells and perhaps other cells throughout the body more susceptible to malignant transformation.

This research has enormous potential for the future of cancer prevention and treatment.
Lung cancer is now one of hundreds of diseases for which a specific gene mutation has been shown to increase the risk of developing an illness dramatically. This includes breast cancer, colon cancer, diabetes and a number of medical conditions that predispose patients to cardiac, pulmonary and neurological diseases. The presence of these gene variants often is used as a screening tool to identify an individual at high risk of developing a specific illness.

For example, there is a well-known series of genes that indicates a dramatic increase in risk in breast cancer. If this series is present in a family with a history of breast cancer, women on occasion may elect to have prophylactic mastectomies because the risk of developing cancer is astronomically high.

In a recent article published in the Journal of the American Medical Association, research has shown that a careful analysis of the genetic characteristics of a specific breast cancer in combination with clinical information from the patient can allow tailor-made therapies that have the potential to increase the chance of cure while minimizing serious complications.

Ideally, this newfound research on lung cancer ultimately will lead to a screening test to identify the gene variant predisposing patients to lung cancer. The presence of the gene could be a wake-up call to smokers or could lead to greater vigilance in looking for early lung cancer. There is also hope that further research will identify avenues to modify this gene directly on chromosome 15, thus reducing the level of dependence and making the individual and those exposed to secondhand smoke less susceptible to the adverse effects of cigarettes.

The recent information on genetic testing for lung cancer risk highlights the incredible breakthroughs that come from basic scientific research. As new findings continue to be uncovered, scientists and physicians have the potential to minimize the risk of developing disease while providing new therapies that have the potential to eradicate cancers altogether.

Dr. David Lipschitz is the author of the book "Breaking the Rules of Aging." To find out more about Dr. David Lipschitz and read features by other Creators Syndicate writers and cartoonists, visit the Creators Syndicate Web page at www.creators.com. More information is available at www.drdavidhealth.com.

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Originally Published on Thursday May 01, 2008

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