Smoking receptors mirror lung cancer genes

A region on chromosome 15 that hosts three nicotine receptor subunit genes is associated with risk of lung cancer, report three papers in Nature and Nature Genetics this week. The results provide some of the strongest evidence so far that lung cancer risk variants are common in the general population, although the groups differ on whether the association is direct or mediated through nicotine dependence.

Although smoking contributes substantially to the risk of lung cancer, it has been known for more than 40 years that there is a genetic component to disease risk too. The three teams find that genetic sequences in the nicotinic acetylcholine receptor subunit gene cluster contribute to susceptibility, although the groups took different paths to this result.

Kari Stefansson’s team find that alleles present in a cluster of nicotinic acetylcholine receptor genes affect smoking quantity in European samples, and are therefore also associated with risk of lung cancer and peripheral arterial disease.

Paul Brennan and colleagues suggest that the susceptibility is not related to smoking status or frequency, and show an association with a specific amino acid change. Christopher Amos and colleagues also test the hypothesis that these variants might increase risk of lung cancer by promoting smoking behaviour, but found that the association with cancer was independent of smoking.

A related News and Views article by Steven Chanock and David Hunter discuss the discrepancy in results, concluding that there should be further research; “When the smoke clears and additional regions are confirmed, we may be in a position to evaluate tailored interventions informed by knowledge of genetic predisposition to smoking initiation or addiction and thus add new powerful weapons to the anti-smoking armamentarium.”