Cancer gene variation 'doubles lung cancer risk' in smokers
Smokers who carry a gene variant found in about 2 per cent of the population have an even higher risk of lung cancer, a large-scale UK-led study has shown.
Scientists found that a specific change in the gene almost doubles the overall risk of lung cancer.
Smokers generally have a 13 per cent life-time risk of lung cancer, meaning that thirteen out of every hundred smokers tend to develop the disease. But this risk rose to 25 per cent if they carried the gene variant. This means that one in four gene carriers would be expected to get cancer if they smoked.
Of the 10 million adults who smoke in the UK, up to 200,000 are thought to fall into this category, the researchers said.
Study leader Professor Richard Houlston, from the Institute of Cancer Research in London, said: "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.
"Lung cancer claims more than a million lives a year worldwide and is by far the biggest cancer killer in the UK. We know that the single biggest thing we can do to reduce death rates is to persuade people not to smoke, and our new findings make plain that this is even more critical in people with an underlying genetic risk."
To find gene variations linked to lung cancer, the scientists scoured existing databases containing information on the DNA of more than 17,000 Europeans with and without lung cancer.
They spotted a specific alteration in the genetic code of BRCA2 known as c.9976T that was more common in people who went on to develop the disease.
A weaker link between lung cancer and changes in another gene, CHEK2, was also identified.
The results, published in the journal Nature Genetics, open up the possibility of personalised treatment for lung cancer patients with BRCA2 mutations.
A family of experimental drugs called PARP inhibitors have shown signs of effectiveness in breast and ovarian cancer patients with defective versions of the gene. However, more trials are needed to ascertain whether these drugs could work against lung cancer.
Earlier this year Cancer Research UK launched a trial to look at using these drugs in lung cancer patients.
Professor Peter Johnson, the charity's chief clinician, said: “We’ve known for two decades that inherited mutations in BRCA2 make people more likely to develop breast and ovarian cancer, but these new findings show a greater risk of lung cancer too, especially for people who smoke.
“Importantly, this research suggests that treatments designed for breast and ovarian cancer may also be effective in lung cancer, where we urgently need new drugs.
Professor Johnson said research into the gene changes within many types of cancer is continuing to yield important information about how cancers develop, and how to find new treatments.
“But, with or without one of these genetic flaws, the single most effective way to reduce the risk of lung cancer is to be a non-smoker,” he added.
The research was supported by a range of organisations, including Cancer Research UK.
Wang Y., McKay J.D., Rafnar T., Wang Z., Timofeeva M.N., Broderick P., Zong X., Laplana M., Wei Y. & Han Y. & (2014). Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer., Nature genetics, PMID: 24880342