First Common Genetic Clue to Lung Cancer

It is a well known fact that cigarettes can cause lung cancer. Even though this fact is well known, some people smoke daily for their whole lives, and never get the disease. Because of this, there was a search for an explanation. Three studies have found a marker in the same region of DNA that seems to increase the chance of lung cancer. Researchers have not decided whether that gene directly causes lung cancer, or if the gene makes it easier for people to get addicted to tobacco. This research is part of a wave of studies that scan the entire genome of hundreds or thousands of people for 300,000 or more DNA markers, and then check whether some markers turn up more often in people with disease than in healthy people.

I chose this topic because I know people who smoked for many years like a chimney, and have never had any lasting effects of cigarettes. Two of these people are my grandpas, and I would like to know if this marker increases or decreases the potential for lung cancer. Also, I would like to know if this marker on a chromosome can be passed down, or if it occurs due to other factors. I know I may sound like a nerd, but I am interested in the human genome and how it correlates to genetic traits.

There was a study done in Reykjavik, Iceland by the researchers at DeCode Genetics, who were hunting for variants in lung cancer, where they scanned the DNA of eleven thousand Icelandic smokers. What the researchers found was a marker on the fifteenth chromosome that is associated with lung cancer, and can cause arteries to narrow. However, the DeCode team has reported that the marker was found most frequently in people who smoke more than thirty cigarettes a day. This suggests that the marker raises the disease risk by making the smoker smoke more frequently.

There is a disparity in this, because there are two other research teams who came to a completely different conclusion. In a paper called Nature, Paul Brennan, who is a part of the International Agency for Research on Cancer in Lyon, France, made a comparison of two thousand Europeans who had lung cancer to an equally sized group of healthy people “non-smokers. Paul Brennan's team also found a DNA marker in the same area on chromosome fifteen. They found that the maker only affected cancer risk, and that it had nothing to do with smoking behavior. Another study concluded the same thing. The smaller study was published in Nature Genetics by a team that the M. D. Anderson Cancer Center in Houston, Texas. In all three of the studies done on the marker, the risk of lung cancer increased. The risk of lung cancer goes from a thirty percent chance with one marker, to between a seventy or eighty percent chance of cancer in people who have two copies of the marker.

The marker sits in a region that consists of three genes that are responsible for the coding of subunits of the nicotinic acetylcholine receptor. The nicotinic acetylcholine receptor is a protein that is on the cell surface that nicotine molecules latch onto, triggering cell change. There are receptors that have a mechanism that could be directly involved in tumor formation. Brennan stated that lab studies have shown that stimulating cancer cells with nicotine or any of its metabolites can spur them to form tumors. If this is the case, the receptors could be a new target for lung cancer drugs, says Brennan.

In addition to this, if the marker actually is involved in nicotine dependency, this finding is going to be very important in the whole field of substance abuse, says Nora Volkov. Nora Volkov is a director of the United States National Institute on Drug Abuse, located in Bethesda, Maryland. The nicotine receptors are active in a part of the brain that is associated with depression. These receptors are not those classically associated with nicotine dependence, Volkov said. They could point researchers to new treatments for tobacco addiction.

The simplest way to summarize the studies is that in chronic smokers, a marker can be added to the fifteenth chromosome because of nicotine molecules attaching to the nicotine acetylcholine receptor. These Nicotine Acetylcholine Receptors trigger cell change, and could be directly involved in tumor formation. The science surrounding a marker on the fifteenth chromosome is still very much inconclusive, but every day we are getting closer and closer to solving the human genome.

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