Around a quarter of smokers who have a particular genetic defect will develop lung cancer at some point in their lifetime, a large international study has found.

A previously unknown link has been found between lung cancer and a defect in the BRCA2 gene, which is best known for its role in breast cancer.

In research published in Nature Genetics, the BRCA2 defect is shown to increase the risk of developing lung cancer by about 1.8 times.

“Smokers in general have nearly a 15 per cent chance of developing lung cancer, far higher than in non-smokers. Our results show that some smokers with BRCA2 mutations are at an enormous risk of lung cancer – somewhere in the region of 25 per cent over their lifetime,” said study leader Professor Richard Houlston.

The study was led by a team at The Institute of Cancer Research in London, but saw contributions from researchers at the US National Institute of Health and other international labs. It compared the DNA of 11,348 Europeans with lung cancer and 15,861 without the disease, looking for differences at specific points in their DNA.

The link between lung cancer and defective BRCA2 – known to increase the risk of breast, ovarian and other cancers – was particularly strong in patients with the most common lung cancer sub-type, called squamous cell lung cancer. The researchers also found an association between squamous cell lung cancer and a defect in a second gene, CHEK2, which normally prevents cells from dividing when they have suffered damage to their DNA.

The results suggest that in the future, patients with squamous cell lung cancer could benefit from drugs specifically designed to be effective in cancers with BRCA mutations. A family of drugs called PARP inhibitors have shown success in clinical trials in breast and ovarian cancer patients with BRCA mutations, although it is not known whether they could be effective in lung cancer.

“These findings indicate that around a quarter of smokers with a specific defect in their BRCA2 gene will develop lung cancer – a disease which is almost invariably fatal. 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,” Dr Houlston said.