Transcript for Smoking, Genetics and Cancer

M. D. Anderson Cancer Center
Cancer Newsline Audio Podcast Series
Date: August 4, 2008
Duration: 0 / 14:05

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Leonard Zwelling, M.D:

Welcome to Cancer Newsline a weekly pod series from the The University of Texas Cancer Center M. D. Anderson Cancer Center in Houston, Texas. The aim of Cancer Newsline is to help you stay current with the news on cancer research and the rapidly changing advanced in cancer diagnosis, treatment and prevention. We also hope to provide you with the latest information on reducing your family risk of being diagnosed with cancer. My name is Leonard Zwelling; I’m a professor of medicine and pharmacology here in M. D. Anderson and today we will be talking with Doctor Chris Amos who is professor in the Department of Epidemiology and Doctor Paul Cinciripini professor and director of the tobacco research and treatment program and deputy chair of the Dept. of Behavioral Sciences about the research and news in the area of smoking, smoking cessation its relation to genetics and more importantly trying to quit. This discussion was inspired by recent research result in the news about the genetic indicator of lung cancer susceptibility in smokers. Most smokers understand the dangers of smoking and its connection to lung cancer but how real is that danger and what does all the research means for former smokers, and the millions addicted and trying to quit.

So here we are with Doctor Amos and Doctor Cinciripini. I will like to start with Doctor Amos give us a little picture of how prevalent is lung cancer and how deadly is it?

Chris Amos, Ph.D:

Lung cancer is the leading cause to death in the U.S. from cancer with about one hundred and seventy five thousand people dying of this disease every year. So it’s a major health concern in the U.S. and many other countries that we would like to reduce the burden. The best way to reduce the burden if people would quit smoking but that is often a challenge for people.

Zwelling:

Are most lung cancer associated with some degree of smoking?

Amos:

Yes, about 85 to 90 percent of lung cancers occur in individuals who have smoked and the risk associated with smoking if you smoke it increases your risk about 14 fold over people who don’t smoke. So that is the fundamental risk factor for lung cancer. And also smoking is a risk factor for many other diseases including many cardiovascular diseases other cancers like bladder pancreatic cancer and other condition like stroke, chronic obstructive pulmonary disease or emphysema. So these are all negative issues that can occur, health concerns from smoking.

Zwelling:

So why should we even bother with the genetics of lung cancer why won’t don’t we just outlaw smoking? Doctor Cinciripini...

Paul Cinciripini, Ph.D:

Well, there is a very strong movement for the last 20 years in this country for tobacco control and issues around dealing with cigarettes and there presence in the population has been discussed. My personal opinion is that I don’t believe that legislation for outlawing cigarettes would work. We tried that with alcohol many years ago and we know what happen there with the institution of the black market. And so on there have been proposals however if the FDA for ensample would regulate tobacco that we could decrease the amount of nicotine in cigarettes over a period of twenty years and in so doing by reducing the amount of nicotine basically sort of wean the population off of nicotine which is the primary psychoactive drug substance in cigarettes and if you took the nicotine out people really not want to smoke cigarettes.

Zwelling:

It sound to me like nicotine is a addictive substance.

Cinciripini:

Very, it’s on a par with opiates with amphetamines with cocaine it stimulates many of the same brain structures all be it by slightly difference pathways, but fundamentally it’s a drug of abuse.

Zwelling:

Back to Doctor Amos for a second. So tell us, "What is the connection between the genetic findings of your study and lung cancer and or addiction to cigarettes?”

Amos:

We preformed a very large study the initial part of it included about 1,200 lung cancer cases that were seen at M. D. Anderson Cancer Center and similar number individuals who didn’t have cancer that we recruited from Kelsey Seybold Clinics and we performed an analysis of about 300,000 single nucleus type polymorphisms these are little road signs in the genome that indicate which people are different from other people so it sort of allows you to just look for subtle variations among individuals that might identify where a genetic factor is.

Zwelling:

So it’s a genetic fingerprint?

Amos:

It’s a genetic fingerprint, so we did the very massive analysis and we where focusing on identifying genetic factors for lung cancer the reason for doing this is that we want to understand what it is within an individual at that make some higher risk then some that appear to be protected from lung cancer to some extent. So as a result of this very large study there we identify several regions that were of interest and we followed up on some of the regions in another set about 3,000 lung cancer cases and about 4,000 people with out lung cancer. Including some other collaborator from the United Kingdom and what we found was that one region on chromosome 15 which contains 3 genes that are involved in nicotine dependence. So this is a very shocking revelation that a gene that affect nicotine dependents also affects has an affect on lung cancer risk.

Zwelling:

There were three studies that was published at the same time, and there was some disagreement among the studies that as whether the actual genetics were linked it to lung cancer or smoking and you in fact think it might be both?

Amos:

Our study says that variations in this region and this gene affect both lung cancer risk and affect smoking behavior. A group from Iceland said that this gene only works through smoking behavior and a group from France said that the genetic factor only work through… only affects lung cancer risk and not smoking. Our study said that both affects are critical but actually the lung cancer affect seem to be stronger then the nicotine dependents.

Zwelling:

So should people who currently smoke or who once smoked have some kind of genetic test as a method of screening them for there likelihood of developing lung cancer?

Amos:

At this point where not at that point, where these genetic markers are informative enough to identify individuals who have high enough risks to benefit from more intensive screening. The best predictor of lung cancer risk remain your own history of smoking, and history of other diseases. We know that emphysema for example is a major risk factor indicating increase risk for lung cancer. So those are the kinds of features that will motivate a physician to do more screening for you.

Zwelling:

Doctor Cinciripini tell me a little more about what these genes code for these…these nicotine receptors. How does this work? Is that part of the addictive process?

Cinciripini:

Absolutely, there been about six or seven different families of nicotine receptors that been identified. What that really means is that these are places on the neurons that bind with a specific type of transmitter. In this case these receptors bind with the acetyl choline that’s something that we make ourselves, it’s in our own bodies. It’s a neurotransmitter. Nicotine is chemically very similar to acetyl choline so these are call nicotine cholinergic receptor sites. When the nicotine hit one of the sites it stimulates the neurons and in many cases depending where that particular receptor is you may have the release of dopamine, norepinephrine, serotonin, and major neurotransmitters that affect people’s mood. Nicotine receptors are widely distributed throughout the body in the central nervous system and the peripheral nervous system. So there is a very wide spread affect of nicotine when it’s taken to the body.

Zwelling:

So it sounds like there are real biochemical markers of dependency in addiction. So when you and I know you does this kind of research try to get people to stop smoking it’s not just a habit. It’s actually very difficult. It’s as hard as getting people off of harder drugs.

Cinciripini:

Thank you for saying that! I hate when people say smoking is a habit. That really applies something quite different, some sort of acquired behavior that easy to change. It’s not, it’s an addictive process and it’s an addictive process because after many years of smoking our brains adapt. There enormously plastic organ that will adapt to the presence of nicotine. It will adapt to nicotine in such a way that normal functioning is associated with the presence the drug. Abnormal functioning is associated with the absence of the drug. Particularly for example: in cognitive functioning and in mood.

Zwelling:

Phil talked about that either one of you Doctor Cinciripini or Doctor Amos it sound like we have gone from the genetics to the bio chemical to the behavioral and in between there is acceptability for lung cancer so it’s a disaster no matter how you look at it. How do you break that? What kind of things do you look at to break that chain of events?

Cinciripini:

Well a treatment that we focus on in established smokers is a combination of behavioral counseling and medication and there are a variety of medications out there that has been used. Beginning with the early or late eighties of nicotine replacement therapy like the patch and the gum and the lozenge all the way up to medications such as Bupropion which is an anti-depressant is now used for smoking cessation. And a new medication called Vereniclin which is one that is specifically design to bind one of those nicotine receptor sites.

Amos:

So the one point that I would like to make is that risk for lung cancer increases the longer you smoke. So if you are a current smoker it is beneficial that you quit as quickly as you can. Another side of this is that it may take several attempts to quit. In fact, in our data if we look at former smokers, how many times it took before they were actually successful. The mean is actually 5 times. So it’s great if you successfully quit the first time but realize if you fail you just have to try again. And it may be very helpful as Doctor Cinciripini says to seek help during the quit process.

Cinciripini:

Yes you want to emphasize. That’s absolutely true is that the norm is making multiple attempts.

Zwelling:

So if we get a medical disease with a genetic and biochemical basis. It’s clearly an addictive process. What if people were interested participating in the work you do Doctor Cinciripini how would they go about doing that? How would they contact you or your program?

Cinciripini:

We have a number of clinical trials that are on-going. Which we are looking at behavior and medication interventions and if they in the Houston area and would like more information to participate they can call 713-792-2265 and they can either leave a message or somebody will answer and we will be happy to talk with them further.

Zwelling:

Very good! In closing I like to thank both of you for coming and coming to talk about this fascinating research that really links genetics, biochemistry and human behavior. Not often you can do that yet, Thank you both for coming!

Listeners if you have any questions about anything you heard today on lung cancer susceptibility, smoking sensations or genetics, please contact ask M. D. Anderson at 1-877-MD-6789 or online www.mdanderson.org/ask. Thank you for listening to this episode of Cancer Newsline again this is a weekly series. Please tune in next week for our next episode of Cancer Newsline.

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