Tag Archives: genetic study

Could Genetics Play a Role in Degrees of Addiction?

As a practicing hypochondriac it was of particular interest to me to learn about a research company in, of all places, Iceland, which is making what could be historic advances in medicine through the study of human genetics.

This company, deCODE genetics, is exploiting a most unusual data base: that of the total population of Iceland where excellent records have been kept since Norwegian and Celtic (Scottish and Irish) settlers arrived there about ten centuries ago. Today there are only slightly more than 300 000 Icelanders, of whom 94 percent are descended from the original settlers. For gene searchers this is, apparently, like a gift from heaven.

It is akin to having a vast private laboratory, enabling research on thousands of volunteers uniquely related in a manner which renders the search for genetic clues to future health problems. For example, more than 50,000 Icelanders, that is one-sixth of the population, participated in research into the disposition to smoking and, for smokers, the inherent risks of contracting diseases linked to nicotine.

Now deCODE is coming up with suggestions that, through the study of human genetic makeup, or our DNA, it can be predicted with accuracy that one will be predisposed to a particular kind of illness or even, as in the case of cigarette smoking, particular types of addiction.

The company’s scientists have established “a clear link between a single-letter variant of the human genome (SNP) and susceptibility to nicotine dependence.”

Such addiction can lead, for example, to lung cancer and peripheral arterial disease (PAD), a common and debilitating constriction of the arteries to the legs.

The odds of this happening to a given individual can be calculated using these genetic techniques.

The research, which also studied smokers in New Zealand, Austria, Sweden, Italy, the Netherlands and Spain, revealed that there is correspondence not only between genetic makeup and the likelihood of addiction but also to the approximate number of cigarettes an addict is likely to smoke daily.

DeCODE has also isolated key genes “contributing to major public health challenges from cardiovascular disease to cancer, genes that are providing us with drug targets rooted in the basic biology of disease”.

smoking cigarettesGiven the incidence in South Africa of dermatological problems such as the deadly cutaneous melanoma (CM) and basal cell carcinoma (BCC) it is interesting to learn that it is not only very fair skin, blue or green eyes, freckles, red hair and exposure to ultraviolet light (obviously prevalent in South Africa) that can expose one to CM and BCC.

Scientists at deCODE have discovered that “a novel, tightly-linked pair of single-letter variants” near a certain gene on chromosome 20 and another on chromosome 11 specifically increases our susceptibility to sunburn and hence to its dangers.

All this should be of enormous future use to the medical profession, although one suspects that our health minister, Manto Tshabalala-Msimang, would probably prefer some quackery or other for guidance rather than the research of serious Icelandic scientists.

Interestingly, the company offers a personal, on-line service for those wishing to explore their genome tree or whatever geneticists call these things. Just log on to www.decodeme.com – although I haven’t done this, so I cannot advise you what to expect.

By the way, this little cutting edge company is listed on the Nasdaq in New York and the stock quote is DCGN. This writer holds no shares.

Source: Stephen Mulholland, Dispatch Online

Researchers Identify Genetic Variant Linked To Nicotine Addiction

NIDA Researchers Identify Genetic Variant Linked To Nicotine Addiction And Lung Cancer – Variant Also Increases Risk For Cardiovascular Disease

Scientists have identified a genetic variant that not only makes smokers more susceptible to nicotine addiction but also increases their risk of developing two smoking-related diseases, lung cancer and peripheral arterial disease.

The research was supported by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH).

The study, published in the April 3 issue of the journal Nature, “highlights the advances that are being made in genetics research, which can now identify gene variants that increase the risk of complex bio-behavioral disorders,” says NIH Director Dr. Elias Zerhouni. “This finding will help us in our efforts to further reduce the scope and devastating consequences of cigarette smoking.”

“These results suggest for the first time that a single genetic variant not only can predispose to nicotine addiction but may also increase sensitivity to extremely serious smoking-related diseases,” explains NIDA Director Dr. Nora Volkow. “Additionally, it points to potential targets for new smoking-cessation medications that may be more effective at helping smokers to quit.”

The variant is closely linked to two of the known subunits of nicotine receptors, the sites on the surface of many cells in the brain and body that can be bound by nicotine. When nicotine attaches to these receptors in the brain, there are changes in cell activity that results in its addictive effects.Carriers of this genetic variant are more likely than noncarriers to be heavy smokers, dependent on nicotine, and less likely to quit smoking. “The variant does not increase the likelihood that a person will start smoking, but for people who do smoke it increases the likelihood of addiction,” says Dr. Kári Stefánsson, the study’s principal investigator and chief executive officer of deCODE Genetics, a biopharmaceutical company based in Reykjavik, Iceland.

The variant was identified through a technique known as genome-wide association, in which DNA samples (from more than 10,000 Icelandic smokers) were analyzed for the presence of more than 300,000 genetic markers. Subsequent investigation showed that carriers of the variant strongly associated with nicotine dependence were also at increased risk for two smoking-related diseases, peripheral arterial disease and lung cancer. The findings were replicated in populations from five European countries and New Zealand. The researchers estimate that the variant explains 18 percent of cases of lung cancer and 10 percent of cases of peripheral arterial disease in smokers.

Nicotine addictionThe same variant was identified as one that increased risk for lung cancer in two other articles appearing in the April 3rd, 2008, issues of Nature and Nature Genetics, partially funded by two other NIH institutes–the National Cancer Institute and the National Human Genome Research Institute.

For more information on Smoking/Nicotine: http://www.drugabuse.gov/DrugPages/Nicotine.html

The National Institute on Drug Abuse

The National Institute on Drug Abuse is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports most of the world’s research on the health aspects of drug abuse and addiction.

The Institute carries out a large variety of programs to inform policy and improve practice. Fact sheets on the health effects of drugs of abuse and information on NIDA research and other activities can be found on the NIDA web site at http://www.drugabuse.gov.

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 http://www.nih.gov.

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.

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

NIH to Fund New Research Study Regarding Exposure to Cigarette Smoke

Smoking Research Studies Exposure to Cigarette Smoke

Researchers at the University of Pennsylvania recently received a $2.3 million grant from the National Institutes of Health for a new study focusing on the chemical changes that occur when the body is exposed to cigarette smoke.

SmokePrevious research has shown that chemical changes in the body can occur after exposure to cigarette smoke and that smoking and exposure to cigarette smoke is the environmental exposure responsible for causing more deaths than any other toxins.

The chemical elements found in cigarette smoke can cause certain types of cancer and have been associated with cardiovascular, pulmonary and pancreatic diseases.

Smokers, non-smokers and even individuals who are in regular contact with secondhand smoke will be screened for the presence of distinctive lipid and DNA biological indicators or chemicals and through additional discovery potential protein indicators in their blood, urine and breath.

These indicators, also known as biomarkers or biochemicals, will be utilized to determine the susceptibility of individuals to tobacco-related lung and cardiovascular problems after exposure to cigarette smoke. The results will hopefully provide reliable data for use in subsequent studies.

“Only one in ten smokers get lung cancer, but the five-year survival rate after diagnosis is only 15 percent,” says Trevor M. Penning, PhD, Director of The Center of Excellence in Environmental Toxicology (CEET). “The question is, how can we intervene earlier to identify people most at risk. We aim to look at the interaction of genetic susceptibility to lung cancer and biomarkers of exposure to cigarette smoke. At the end of the day, if we study genetics and exposure together, we’ll hopefully have a very strong statement to say who is most at risk.”

Source: Brenda Fulmer, Claris Law
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