Smokers With BRCA2 Mutation Have Increased Risk of Developing Lung Cancer
Around a quarter of smokers who carry a mutation in the BRCA2 gene will develop lung cancer at some point in their lifetime, a large-scale, international study reveals. Scientists described a previously unknown link between lung cancer and a particular BRCA2 mutation, which occurs in around 2% of the population, in new research published in Nature Genetics. The defect in BRCA2 increases the risk of developing lung cancer by about 1.8 times.
Smokers as a group have a lifetime risk of developing lung cancer of around 13% (16% in men and 9.5% in women). The new study therefore suggests around one in four smokers with the BRCA2 defect will develop lung cancer.
Study Findngs
The researchers, led by a team at The Institute of Cancer Research, London, 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 BRCA2 mutations—known to increase the risk of breast, ovarian, and other cancers—was particularly strong in patients with squamous cell lung cancer, the most common lung cancer subtype.
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.
Implications
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. 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.
Study leader Richard Houlston, MD, PhD, Professor of Molecular and Population Genetics at The Institute of Cancer Research (ICR), said, “Our study showed that mutations to two genes, BRCA2 and CHEK2, have a very large effect on lung cancer risk in the context of smoking. Mutated BRCA2 in particular seems to increase risk by around 1.8 times.
“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,” he added.
Dr. Houlston and Maria Teresa Landi, MD, PhD, of the National Institutes of Health, are the corresponding authors for the Nature Genetics article.
The research was funded in part by the National Institutes of Health and Cancer Research UK.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
