Evidence for a genetic link to lung cancer

Scientists have found evidence that there is a strong genetic link to lung cancer. The findings, from three teams in Iceland, France and the US, will help understanding of the genetic basis of the disease and the role tobacco plays in its development.

Lung cancer is the most common killer of all cancers, with more than one million cases worldwide diagnosed annually. Until now, the cause was thought to be largely environmental - tobacco smoking. These results however, reported online in the journal Nature Genetics, show for the first time that a genetic variation could predispose a person to the disease.

The researchers carried out a two-stage genome-wide association study on 11,000 smokers in Iceland and 32,000 lung cancer patients from around the world. They looked at frequencies of 'SNPs', which are single-letter variants in the DNA. A region on chromosome 15 was pinpointed where SNPs were found to be associated with the disease. The region contains genes for nicotinic acetylcholine receptors, which interact with nicotine and other tobacco toxins. About 50 per cent of the population have one allele with the variant, which raises the risk of lung cancer by about 30 per cent. If a person has two copies of the variant, however, the risk of developing the disease can increase to 80 per cent.

Despite the unequivocal evidence of the genetic link, the groups disagree over whether having the DNA variants predisposes people to lung cancer directly, or indirectly, by increasing addiction to cigarettes. Paul Brennan, of the International Agency for the Research on Cancer in Lyon, France, and Dr Christopher Amos who led the US study at the University of Texas M.D. Cancer Center, believe that there is no evidence that the genetic effect depends on nicotine intake, so the risk of the disease is independent of smoking. 'Any association with nicotine must be modest' says Brennan, and he adds that 'a lot more work is required in this area'.

Kari Stefansson of deCODE Genetics in Reykjavik, Iceland, who led the third study, believes that the genes make people more vulnerable to nicotine addiction, thereby promoting cancer.

Anti-smoking campaigners stress that smoking is still the number one risk factor for lung cancer. 'It's important to remember that the best thing a smoker can do to reduce their risk of lung cancer and a host of other life-threatening diseases is to quit', says Lesley Walker, director of cancer information at Cancer Research UK.