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. 2008 Apr 3;452(7187):638-642.
doi: 10.1038/nature06846.

A Variant Associated With Nicotine Dependence, Lung Cancer and Peripheral Arterial Disease

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Free PMC article

A Variant Associated With Nicotine Dependence, Lung Cancer and Peripheral Arterial Disease

Thorgeir E Thorgeirsson et al. Nature. .
Free PMC article

Abstract

Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases.

Comment in

  • Genomics: when the smoke clears ..
    Chanock SJ, Hunter DJ. Chanock SJ, et al. Nature. 2008 Apr 3;452(7187):537-8. doi: 10.1038/452537a. Nature. 2008. PMID: 18385720 No abstract available.

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