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Genes R US — The biochemistry of cigarette smoking suggests a healthier alternative

Genes R US — The biochemistry of cigarette smoking suggests a healthier alternative

Posted: Wednesday, August 22, 2012 5:00 pm

George Miller died when I was 28. I can still see him sitting at the dining room table smoking Camel™ cigarettes, his fingers stained brown from a lifetime of smoking. He continued to smoke for years after he was tethered to a big green tank of oxygen.
Dad knew it was dangerous to smoke while his oxygen was flowing, but the deep satisfaction he experienced when he lit-up somehow made that risk acceptable. That image of Dad, smoking while on oxygen, epitomizes the strength of the addiction of cigarette smoking. 
Dad struggled with emphysema in every memory that I have of him; he was completely unable to work by the time I was 12.  The “CC” genotype for the SNP, rs11536889, increases the risk of developing emphysema by 2.6 times in smokers. This single point DNA variation is found in a gene called TLR4 for the innate immune system. Maybe Dad had this SNP. 
Studies using more than 17,000 twins estimated that genetic factors account for 56 percent of the variance in starting smoking and regular use. Environmental risk factors account for 24 percent, while individual risk factors account for the remaining 20 percent. (
The Center for Disease Control estimated that 21 percent of adults in the United States smoked cigarettes in 2009, a number equaling 46 million people.  
People associate smoking with control of weight, but smoking predisposes one to develop the most dangerous kind of fat — right around the middle — and increases the risk for glucose intolerance and insulin resistance.
There are two biochemical aspects to smoking (1) the carcinogenic compounds in the smoke and (2) the addictive nature of nicotine. 
The vast majority of cancers, 90-95 percent, are caused by, or closely associated with, environmental factors and lifestyle. This includes diet (30-35 percent), cigarette smoking (25-30 percent), and alcohol consumption (4-6 percent). (
Cigarette smoking stimulates the inflammatory response by elevating levels of proteins called cytokines, such as TNF-_ and IL6, which are associated with the development of all the diseases related to smoking. (
Smoking tweaks our genes by (typically) down-regulating the biochemical keys that initiate the process of transcribing genes to make proteins. This plays dangerously with a whole host of biological processes, especially those that govern tumor growth. 
Now no one smokes because they believe it is healthy or harmless. Rather they smoke because it makes them feel better. It does this by impacting the neurotransmitters of the brain. 
Cigarette smoking stimulates the production of brain chemicals called opioids, which soothe pain and increase positive emotions and feelings of reward and a sense of well-being. Mice without mu-opioid receptors in the brain can’t become addicted to nicotine.
Nicotine triggers the release of addictive “feel-good” brain chemicals just like morphine and heroin. 
Nicotine also increases the release of serotonin from the brain, and it decreases its reuptake in the part of the brain called the hippocampus. Serotonin is the happy and calming hormone. Together, these effects make available a greater amount of serotonin, which ultimately stimulates dopamine release.
The actual addiction is from the dopamine action of the nicotine. During withdrawal from nicotine, serotonin release is dramatically reduced which is why people are crabby when they are quitting smoking.
Many of the folks smoking should be on anti-anxiety or anti-depressants — but they may not be comfortable “taking drugs.” Instead they elect to self-medicate with cigarettes. They believe they have found something that works.
Researchers have demonstrated that they can tweak people’s urge to smoke with medications that stimulate or block their dopamine receptors. Some drugs like Zyban (bupropion) increase circulating dopamine in brain, while others like Chanex (varenicline) decrease the pleasure from smoking itself.
You can’t scare or talk someone into quitting smoking. I saw that with my own father. Many smokers are self-medicating a shortcoming in how their brains create and utilize serotonin and dopamine. What is their motivation to quit? They feel good when they smoke. 
And if they do quit, the underlying brain problem remains. There are FDA approved drugs that will actually help heal the smoker’s brain. They have a strong safety profile. And those meds will cost less money and add years of quality onto the smoker’s life. 
Editor’s note: Nancy@ has worked in scientific research and development for 27 years. She blogs at

Published in The Messenger 8.22.12

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