Tag Archives: genes cigarette addiction

Genetic Achilles Heel May Support Nicotine Addiction

Do genes play a role in tobacco addiction?

Recent studies suggest they may, particularly the CHRNA5 gene.

A University of Michigan press release notes a genetic variation suggests a finding that may help explain the path that leads from that first cigarette to lifelong smoking.

In the press release studies smokers and non-smokers to find if you have the less common rs16969968 form of the CHRNA5 gene and you smoke a cigarette you are more likely to get hooked.

Yet another reduction in the possible scope for free will.

Study on Genetics, Genes and Smoking

In a paper published in the September Issue of the journal Addiction, a multi-university collaborative team of researchers specializing in statistical genetics, gene analysis, and trait analysis reports an association between a variant in the CHRNA5 nicotine receptor gene, initial smoking experiences, and current smoking patterns.

The genetic and smoking data come from 435 volunteers. Those who never smoked had tried at least one cigarette but no more than 100 cigarettes in their lives, and never formed a smoking habit. The regular smokers had smoked at least five cigarettes a day for at least the past five years.

The regular smokers in the study were far more likely than the never-smokers to have the less common rs16969968 form of the CHRNA5 gene, in which just one base-pair in the gene sequence was different from the more common form. This kind of genetic variation is called a single nucleotide polymorphism or SNP.

Smokers were also eight times as likely to report that their first cigarettes gave them a pleasurable buzz.

“It appears that for people who have a certain genetic makeup, the initial physical reaction to smoking can play a significant role in determining what happens next,” says senior author and project leader, Ovide Pomerleau, a professor of psychiatry at the University of Michigan Medical School and founder of the U-M Nicotine Research Laboratory.

“If cigarette smoking is sustained, nicotine addiction can occur in a few days to a few months,” he adds. “The finding of a genetic association with pleasurable early smoking experiences may help explain how people get addicted — and, of course, once addicted, many will keep smoking for the rest of their lives.”Among those who ever try smoking this gene explains only part of the difference between those who become addicted and those who do not. Expect more discoveries of genes that contribute to the odds of getting addicted.

Achilles HeelWe are witnessing an acceleration of the rate of discovery of genetic factors that influence behavior. This acceleration in the rate of discovery will accelerate as DNA testing costs continue to drop. So expect to see many more reports of genes that influence behavior.

Source: Randall Parker, FuturePundit

Smoking’s Effects on Genes May Play a Role in Lung Cancer Development and Survival

Smoking plays a role in lung cancer development, and now scientists have shown that smoking also affects the way genes are expressed, leading to alterations in cell division and regulation of immune response.

Notably, some of the changes in gene expression persisted in people who had quit smoking many years earlier.

These findings by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, appeared in the Feb. 20, 2008, issue of PLoS ONE.

“Smoking, we are well aware, is the leading cause of lung cancer worldwide,” said NCI Director John E. Niederhuber, M.D. “Yet, a mechanistic understanding of the effects of smoking on the cells of the lung remains incomplete. This study demonstrates an important piece of this complicated puzzle. Greater understanding of the genetic alterations that occur with smoking should provide greater insight into the development of cellular targets for treating, and possibly preventing, lung cancer.”

“We were able to look at actual lung tissue, tumor and non-tumor, taking into account the differences by gender, verifying the smoking status by measuring levels of cotinine, a metabolite of nicotine, in participants’ plasma, and confirming results in independent samples,” said Maria Teresa Landi, M.D., Ph.D., in NCI’s Division of Cancer Epidemiology and Genetics, the first author of the study report.

To investigate the effects of smoking on gene activity in lung tissue, the researchers examined the gene expression profiles — patterns of gene activity — in early-stage lung tumors and non-tumor lung tissue of smokers, former smokers, and people who had never smoked cigarettes. Gene expression was measured in 58 fresh-frozen tumor and 49 fresh-frozen non-tumor samples from 74 participants of the Environment And Genetics in Lung cancer Etiology (EAGLE) study, a large lung cancer study that was conducted in the Lombardy region of Italy.

Adenocarcinoma tumor samples were evaluated in this study because adenocarcinoma is the most common type of lung cancer, and it occurs in both smokers and people with no history of smoking. The participants were 44 to 79 years of age, and 28 were current smokers, 26 were former smokers, and 20 had never smoked. The researchers also obtained detailed medical information about the participants (for example, whether individuals had previous lung diseases or chemotherapy) and biochemically confirmed participants’ smoking status.

Using microarray techniques, which allow researchers to look at the activity of thousands of genes simultaneously, they identified 135 genes that were differently expressed in tumors of smokers vs. people who had never smoked. Among these genes, 81 showed decreased expression and 54 showed increased expression in tumor tissue.

Most of the genes showing significantly increased expression, e.g., TTK, NEK2, and PRC1, are involved in cell cycle regulation and mitosis. The cell cycle is a step-wise sequence of events in which a cell grows and ultimately divides to produce two progeny, or daughter, cells. During the cell cycle, the chromosomes of the parent cell are duplicated and then, in a step called mitosis, divided equally between the daughter cells, ensuring that each daughter cell inherits a complete set of chromosomes. The cell apparatus responsible for the proper division of chromosomes is called the mitotic spindle.

Picture of Lungs“Our results indicate that smoking causes changes in genes that control mitotic spindle formation,” said Jin Jen, Ph.D., in NCI’s Center for Cancer Research, a senior author of the study report. “Irregular division of chromosomes and chromosome instability are two common abnormalities that occur in cancer cells when the chromosomes do not separate equally between the daughter cells. Therefore, changes in the mitotic process are very relevant in the development of cancer.” Several of the identified genes have been suggested in the past as potential targets for cancer treatment.

The researchers also found similar expression of many genes among current smokers and former smokers in tumor tissue. Several of these genes, such as STOM, SSX2IP, and APLP2, remained altered in participants who had quit smoking more than 20 years before the study. Therefore, smoking seems to cause long-lasting changes in gene expression, which can contribute to lung cancer development long after cessation.

Looking at non-tumor lung tissues, the team found decreased activity for 73 genes and increased activity for 25 genes in current smokers. The genes most affected by smoking play a role in immune response-related processes, possibly as a lung defense mechanism against the acute toxic effects of smoking. However, non-tumor tissues seem to be able to recover from the effects of smoking. The researchers did not identify significant changes in the immune response-related genes in former smokers.

To gain a better understanding of the impact of smoking-related changes in gene expression on lung cancer survival, the researchers compared the overall gene expression smoking profile in lung tumor and non-tumor tissues with survival. They found that the altered expression of the cell cycle-related genes NEK2 and TTK in non-tumor tissues was associated with a three-fold increased risk of lung cancer mortality in smokers.

“Our data provide clues on how cigarette smoking affects the development of lung cancer, indicating that the very same mitotic genes known to be involved in cancer development are altered by smoking and affect survival. More studies are needed to confirm that the gene expression changes are due to smoking and affect tumor development or progression,” said Landi. “If confirmed, these genes could become important targets for preventing and treating lung cancer.”

About 90 percent of lung cancer deaths among men and almost 80 percent of lung cancer deaths among women can be attributed to smoking. In 2006, approximately 20.8 percent of U.S. adults were cigarette smokers. Cigarette smoking remains the leading preventable cause of death in the United States, causing an estimated 438,000 deaths, or about one out of every five deaths each year.

For more information on research in Dr. Landi’s group, please go to http://dceg.cancer.gov/about/staff-bios/landi-maria.

For more information about the EAGLE study, please go to http://dceg.cancer.gov/eagle.

For more information about cancer, please visit the NCI website at http://www.cancer.gov/, or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.


Reference:
Landi MT, Dracheva T, Rotunno M, Figueroa, JD, Liu H, Dasgupta A, Mann FE, Fukuoka J, Hames M, Bergen AW, Murphy SE, Yang P, Pesatori AC, Consonni D, Bertazzi PA, Wacholder S, Shih JH, Caporaso NE, and Jen J. February 2008. Gene Expression Signature of Cigarette Smoking and Its Role in Lung Adenocarcinoma Development and Survival. PLoS ONE. Vol. 3, No. 2.

Crazy Cravings May Be Genetic

Individual brain chemistry and genes could be the key to understanding why some people become addicted to nicotine, University of Colorado at Boulder researchers say.

The depth of a person’s addiction to nicotine appears to depend on his or her unique internal chemistry and genetic make-up,  said lead author Jerry Stitzel, an assistant professor in CU-Boulder’s department of integrative physiology and researcher with CU-Boulder’s Institute for Behavioral Genetics.

It’s also why the chemical compound’s effects appear to diminish at night, said Stitzel, who presented his team’s findings in San Diego last week during the Neuroscience 2007, an annual scientific meeting.

Stitzel and his team set out to evaluate the effects of nicotine over the course of a day by examining mice that could make and “recognize” melatonin, a powerful hormone, and others that could not.

Scientists believe that melatonin, which is produced by darkness, tells our bodies when to sleep. The CU researchers found that the reduced effects of nicotine at night were dependent on the mice’s genetic make-up, and whether their brains and bodies were able to recognize melatonin.

Crave ImageThey also found that the daytime effects of nicotine were greatest when levels of the stress hormone corticosterone were high.

The second finding could explain why many smokers report that the first cigarette of the day is the most satisfying.

Cortisol, the human equivalent of corticosterone, is at peak levels in the early morning, Stitzel said.

“The negative health consequences of smoking have become well known, and a large majority of smokers say that they would like to quit,” Stitzel said. “As such, we need to understand the interaction between smoking, genes and internal chemistry so we can target new therapies to those who have a hard time quitting.”

While the team’s research could shed light on why people smoke, Stitzel says more research is needed to determine the role that melatonin plays in altering the effects of nicotine, and whether the correlation between higher corticosterone levels and nicotine sensitivity is a coincidence.

Researchers from Yale, Florida State, the University of Minnesota and the Baylor College of Medicine also presented findings based on research into the effects of smoking and nicotine.

Source: Colorado Daily

Corticosterone, Genetics And The Addiction Of Nicotine

Individual brain chemistry and genes could be key to understanding why some people become addicted to nicotine and why the chemical compound’s effects appear to diminish at night, University of Colorado at Boulder researchers say.

“The depth of a person’s addiction to nicotine appears to depend on his or her unique internal chemistry and genetic make-up,” said lead author Jerry Stitzel, an assistant professor in CU-Boulder’s department of integrative physiology and researcher with CU-Boulder’s Institute for Behavioral Genetics.

He and his team set out to evaluate the effects of nicotine over the course of a day by examining mice that could make and “recognize” melatonin, a powerful hormone and antioxidant, and others that could not. Scientists believe that melatonin, which is produced by darkness, tells our bodies when to sleep.

The CU researchers found that the reduced effects of nicotine at night were dependent on the mice’s genetic make-up and whether their brains and bodies were able to recognize melatonin. They also found that the daytime effects of nicotine were greatest when levels of the stress hormone corticosterone were high.

The second finding could explain why many smokers report that the first cigarette of the day is the most satisfying. Cortisol, the human equivalent of corticosterone, is at peak levels in the early morning, Stitzel said.

“The negative health consequences of smoking have become well known, and a large majority of smokers say that they would like to quit,” Stitzel said. “As such, we need to understand the interaction between smoking, genes and internal chemistry so we can target new therapies to those who have a hard time quitting.”

While the team’s research could shed light on why people smoke and how nicotine affects them, Stitzel says more research is needed to determine the role that melatonin plays in altering the effects of nicotine, and whether the correlation between higher corticosterone levels and nicotine sensitivity is a coincidence.

The CU-Boulder study was funded by the National Institute on Drug Abuse, a part of the National Institutes of Health.

CorticosteroneResearchers from Yale, Florida State, the University of Minnesota and the Baylor College of Medicine also presented findings based on research into the effects of smoking and nicotine.

Among their conclusions: Smoking may predispose adolescents to mental disorders in adolescence and adulthood; a network of neurons, or cells in the nervous system, may regulate the body’s craving response; and smoking may affect decision-making.

– University of Colorado at Boulder

*Thanks goes to Cuckoo from AS3 for submission to CF.

COPD & Facial Wrinkling Study

The presence, and perhaps the severity, of COPD might be predictable by examining the facial skin, and accelerated wrinkling could signal the need for studies of lung function.

Smoking is associated with other health-related problems, and future studies might attempt to correlate skin findings with cardiovascular disease in smokers.

Laboratory elucidation of the specific mechanism behind increased susceptibility would be useful and interesting.

Picture of Wrinkled Face from SmokingIf a genetic predisposition is identified, susceptible families and individuals might receive more urgent counsel to avoid smoking and exposure to secondhand smoke.

Learn more about > COPD.

— Jeffrey P. Callen, MD

Gene Links Alcoholism, Tobacco Addiction, Stress

A team of Quebec researchers has uncovered a series of genes linking the response to stress and high blood pressure with alcoholism and tobacco dependence.

If a person has that series of genes, he or she will be more prone to drink or smoke in order to cope with stress and high blood pressure, according to researchers.

“What that tells us is that it’s not only bad education or family behaviour that matters,” explained Dr. Pavel Hamet, who is leading the study of 120 families in the Saguenay Lac-St.-Jean region.

“The fight against alcohol and tobacco should not only be moralistic, but also give people ways to manage stress,” he said, adding that one in five persons has the predisposition.

He gave his findings at the Canadian Cardiovascular Congress in Quebec City yesterday.

Alcohol and TobaccoHamet believes this discovery could explain why men are more prone to alcohol abuse than women.

His team found that the genes that govern alcohol intake appear on chromosome X. Men only have one chromosome X, while women have two.

“A man can only get his chromosome X from his mother, so he is more at risk than the woman who gets one from her mother and one from her father,” said Hamet, director of research at the University of Montreal Hospital Centre.

Hamet believes this study could be helpful to help high-risk people reduce stress and blood pressure, often leading to heart diseases and higher risks of getting a stroke.

Source: The Vancouver Province

Cigarette Smoking and the Human Spine

Smoking effects the flow of blood throughout our bodies.

There are only two structures in the adult human body which, under normal circumstances, lack a blood supply in adult life.

One, the cornea of the eye which gets its nutrition from tears.

Secondly, the intervertebral disc, which obtains its nutrition from the convection and diffusion of nutrients from the end plates of adjacent vertebral bodies.

Picture of the SpineBy smoking cigarettes, nicotine and carbon monoxide infuse into the blood stream and then into body tissues.

These poisons have a particularly destructive effect on intervertebral discs (and corneas) because of their precarious nutritional status.

Read the rest of the Burton Report here > Smoking Cigarettes Effects on the Human Spine