25 October 2010
By Akanksha Bafna
Mumbai, India
New research has revealed that a gene is responsible for how much a person smokes and whether s/he is at high risk of developing lung cancer, or chronic obstructive pulmonary disease (COPD).
The research was carried out at the University of Washington’s School of Medicine in St Louis, as the first large–scale effort to match genetics with smoking, lung cancer and COPD combined.
The investigators studied 38,000 smokers and found that two groups of gene variants on chromosome 15 influence risk for all three problems.
"We put together a consortium from around the world and analysed DNA variants that caused biological changes in smokers," said Laura Jean Bierut, senior investigator of the study.
"We were able to demonstrate that both of the variants affect the amount a person smokes. Then we showed that the same pattern of variants contributes to lung cancer and COPD," Bierut said.
Nicotine, the main, addictive ingredient in cigarettes, binds to nicotinic receptors in cells. Past genetic studies have implicated a section of chromosome 15 that includes important nicotinic receptor genes, and in this study, the investigators looked specifically at those genes (CHRNA5, CHRNA3 and CHRNB4).
Various forms of the nicotinic receptor genes were associated with how much a person smoked, and not surprisingly, heavy smokers turned out to be at greatest risk for lung cancer and COPD.
"Previous studies have shown associations between gene variants and smoking," said Nancy Saccone, lead author of the study.
"The important finding from our analysis was that a new group of variants also is associated with smoking behaviour, further highlighting this area as an important target for follow–up studies to better understand the mechanisms underlying those associations we observed."
The study revealed that DNA differences on chromosome 15, particularly in the CHRNA5 nicotine receptor gene, made significant contributions to nicotine addiction, lung cancer and COPD.
"Demonstrating that all three variants are related to smoking behaviour does not prove that there is a direct, biological effect linking nicotine addiction to cancer and COPD, but you certainly can’t rule it out," Bierut said.
"It’s really striking that this one gene is strongly driving addictive behaviour and is also related to lung cancer and COPD."
The CHRNA5 gene functions both in the lung and in the brain. It is active in regions of the brain involved in addictive behaviour.
"There is a reward centre in the brain," Bierut said. "The centre becomes activated with addiction, and the gene is clearly active in that brain region.
"But the gene also functions in the lung, meaning we need to ask the question whether this gene [CHRNA5] is both driving the pathology of addiction in the brain while also working in the lung to contribute to COPD and cancer."
The gene sequence differed in light–smoking people who smoke fewer than 10 cigarettes a day from heavy smokers who light up more than more than 20 times daily.
Depending on which gene variants a person has, the individual will tend to smoke different amounts. People respond to nicotine differently, based in part on their genetic makeup, and then they adjust the amount they smoke according to nicotine’s addictive effects.
"What we have identified in this study was detectable only after we accounted for the effects of other genetic variants in the same region of chromosome 15," Saccone said.
The findings appeared in the journal Public Library of Science (PLoS) Genetics.
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