More evidence that genes increase a smokers' risk of lung cancer

Cancer Research UK funded scientists have confirmed that inherited changes in certain regions of the genome can increase a smokers' risk of developing lung cancer lung cancer, and determine the type of lung cancer that develops. Their results were published in this week's edition of the journal Cancer Research*.

The researchers at The Institute of Cancer Research scanned the genomes of 1,900 lung cancer patients and compared them to 1,400 healthy individuals to identify specific changes in the DNA that were linked with an increased risk of lung cancer.

They then scanned the genes of a further 2,000 lung cancer patients for these changes and compared these to a similar number of healthy people.

This identified changes in three regions of the genome which were more common in lung cancer patients than healthy individuals. These regions sat on chromosomes 5, 6, and 15, implicating these regions in lung cancer.

Their work shows more complexity than originally thought for the chromosome 15 association. Specifically the association involves two independent sites that could play a role in lung cancer. Previous research has shown that variation at these two sites influence lung cancer risk and these findings confirm this.

This work had calculated that current or former smokers who carry one copy of each variant increase their risk of lung cancer by 28 per cent while current or former smokers who carry two copies of each variant increase their risk by 80 percent. While people who do not smoke can also carry these changes the risk is only increased in those that smoke.

These variants are located in a family of genes that influence smoking behaviour and consumption of tobacco. In addition this set of genes also influences cell growth and cell death.

Lead author Professor Richard Houlston, a Cancer Research UK funded scientist at The Institute of Cancer Research, said: "This research confirms work done at the ICR and elsewhere that has previously implicated these areas in lung cancer risk and the type that develops. The next step is to dig deeper to pin point which gene, or genes in these regions, cause the increased risk of developing lung cancer and how they actually trigger this increase."

The researchers found that the variation at chromosome 5 influenced the type of lung cancer that developed. Those that carried this variant are more likely to develop a subtype of non-small cell lung cancer (NSCLC) called adenocarcinoma, which accounts for 27 per cent of lung cancers in the UK and is the most common type of lung cancer in non-smokers.

The final region identified on chromosome 6 could influence the type of NSCLC that develops, either adenocarcinoma or squamous cell carcinoma.

Dr Lesley Walker, director of cancer information at Cancer Research UK, said: "Smoking greatly increases the risk of lung cancer – causing nine out of ten cases of the disease. This research shows that inherited genetic variation accounts for some of this risk and the type of lung cancer that develops.

"It's important to remember that smoking also increases the risk of other life-threatening diseases including heart disease, stroke and a dozen other cancers. The best thing a smoker can do to reduce their risk of lung cancer, and a range of other life-threatening conditions, is to quit."

* Houlston, R.S. et al. Deciphering the impact of common genetic variation on lung cancer risk: A genome-wide association study Cancer Research 15 August 2009