Mutations in the BRCA2 gene have long been linked to increased risk of developing breast,ovarian and prostate cancers. Now, researchers have found that that a specific variant of the gene also increases the risk of lung cancer, particularly in smokers. Lifetime risk for developing lung cancer for smokers, normally at around 13 percent, rises to 25 percent for those that possess the defective gene.
This means that smokers with this mutant BRCA2 have a one in four chance of developing cancer – almost double the risk of those who don't smoke. The mutant gene is present in about two percent of the population, so given that there are 10 million adult smokers in the UK, the researchers estimate that up to 200,000 people could be affected.
'Our study showed that mutations to [BRCA2] have a very large effect on lung cancer risk in the context of smoking', said Professor Richard Houlston from the Institute of Cancer Research in the UK, one of the lead researchers. 'Some smokers with BRCA2 mutations are at an enormous risk of lung cancer – somewhere in the region of 25 percent over their lifetime', he added.
In the study, published in Nature Genetics, the researchers compared the DNA of over 11,000 lung cancer patients with that of almost 16,000 healthy controls, all of European ancestry, and looked for differences between the two groups. They found that the variant of BRCA2 known as c.9976T was more common in the patients with lung cancer than without, particularly in squamous cell lung cancer, the most common lung cancer type.
It is thought that mutant BRCA2 can no longer properly repair damaged DNA caused by smoking. 'In the context of smoking there is such an enormous amount of DNA damage that any loss of DNA repair is going to be an issue', Professor Houlston told BBC News.
Specific drugs for breast or ovarian cancer patients with BRCA2 mutations are in development and have already shown promising results in clinical trials. This raises the possibility that these drugs, called PARP inhibitors, may also work in lung cancer patients with mutant BRCA2. However, this is only speculative, as whether the drugs will actually work against lung cancer is not known.
This study confirms that there is an inherited genetic susceptibility to lung cancer. Professor Paul Workman, from the Institute of Cancer Research, said: 'All smokers are taking a considerable risk with their health, regardless of their genetic profile, but the odds are stacked even more heavily against those with this genetic defect who smoke'.