genetic variation and lung cancer

Variation in the human genome and the consequences for health are giving exciting result, largely through genome-wide association studies (GWAS). Such studies need to be large and repeatable.. Since early 2007, variations at nearly 100 regions of the genome have been associated with an increased risk for diseases with a complex genetic background, such as diabetes, inflammatory bowel disease, cancer (most notably breast, colorectal and prostate) and heart disease.
Lung cancer is associated with smoking and hence has a considerable environmental factor in its aetiology. Not everyone who smokes heavily gets lung cancer Three recent studies identify variation in the same region of the long arm of chromosome 15 (15q24/15q25.1) as having a key role in the aetiology of lung cancer. Among the genes in this region are those that encode subunits of nicotinic acetylcholine receptors, which have an affinity for nicotine. The genetic variation are as single nucleotide polymorphisms (SNPs, with DNA sequence variations that arise from the substitution of one nucleotide base for another, and contribute approximately 90% of common variation in the human genome.
The three studies are all large and appropriately replicated, but they differ on whether the connection is direct or mediated via smoking behaviour — that is, characteristics such as the duration and ‘dose’ of lifetime smoking, and/or the propensity for nicotine addiction. Previous studies ‘had identified the genes encoding subunits of nicotinic acetylcholine receptors as strongly associated with smoking behaviour. The association between smoking and lung cancer is very strong , and any gene variant that is modestly linked with smoking behaviour will seem to be associated with lung cancer unless the matching of cancer cases and controls by smoking behaviour is close to perfect.
The reports vary in their interpretation of the results. One says that the association between the SNP variations is with the number of cigarettes smoked per day and a nicotine dependence scale. They argue that the link with cancer is though nicotine dependence.
The other two groups interpret their results as an association with lung cancer and not smoking.
These result s indicate the complexity of the subject. It is also indicates that it is easy to jump to conclusions about the aetiology of disease and environmental influences.
Nutrition studies are not sufficiently careful in this area.
Chanock and Hunter 2008 When the smokes clears Nature vol 452, pp 537-538

Martin Eastwood
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