Thursday, April 3, 2008

The Genetics of Cigarettes

Mutations on chromosome 15 linked to lung cancer.

A variation among the genes that code for nicotine receptors in the brain has been linked with increased cigarette smoking and a heightened risk for lung cancer, according to three new studies released this week.

Two studies in Nature, and one in Nature Genetics, demonstrated that people who inherited the genetic variation, or allele, from one parent—roughly 50 percent of the population--had a 30 percent higher risk of developing lung cancer. “What’s more,” according to Michael Hopkin at Nature News, “another 10 percent of the population is likely to carry two copies of this set of mutations, raising cancer risk by as much as 80 percent relative to people with equivalent lifestyles without the cancer-linked gene variant.”

More than 35,000 Caucasian smokers in Europe and North America took part in the government-funded research. It was the strongest evidence to date of a firm link between genetics and lung cancer. It was also added evidence for the existence of biological proclivities in addicted cigarette smokers.

Earlier studies had demonstrated that having a parent or sibling with lung cancer could triple the odds of developing the disease. But teasing out the precise genes responsible has been, as always, a frustrating hunt.

Christopher Amos of the University of Texas, author of one of the studies, characterized the variant as “kind of a double whammy gene” in an Associated Press article by Seth Borenstein. Amos said of the nicotinic acetylcholine receptor gene alleles on chromosome 15: “It also makes you more likely to be dependent on smoking and less likely to quit smoking.” In the same article, psychiatry professor Dr. Laura Bierut of Washington University in St. Louis said that the three studies are “really telling us that the vulnerability to smoking and how much you smoke is clearly biologically based.”

Study author Kari Stefansson of Iceland’s deCode Genetics believes strongly that the genetic variation in question makes people more susceptible to nicotine addiction, and increases the difficulties of quitting: “In our study, we found if you have one allele you smoke about one more cigarette per day; if you have 2 alleles you average two more cigarettes per day.”

However, according to Denise Gellene of the Los Angeles Times: “The studies were divided on whether the genetic variant directly increased the risk of lung cancer or did so indirectly by predisposing people to smoking.” In a third study, Paul Brennan of the International Agency for Research on Cancer in Lyon, France noted no evidence of a link between the rogue gene and nicotine addiction itself.

It is not clear whether non-smokers with the mutation suffer an increased risk of lung cancer as well. (However, even smokers who lack the gene variant are still ten times as likely to develop lung cancer than nonsmokers).

About one million people die annually from lung cancer. According to the World Health Organization, smoking is the leading cause of preventable death worldwide.

Graphics Credit: Technology Review

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