12 June 2014
There are hundreds of known mutations in the BRCA2 gene, many of which are known to greatly increase the risk of breast cancer; the BRCA2 gene is involved in normal DNA repair, and mutations in the gene have also been linked with increased risk of various other cancers, including ovarian and prostate cancer, but this is the first association with lung cancer.
Published in peer-reviewed journal Nature, the research involved a meta-analysis of four genome-wide association studies in European populations, comparing data from individuals with and without lung cancer. They identified a number of genetic variants associated with increased risk of disease, including two rare variants with marked effects on risk in the cancer-associated genes BRCA2 and CHEK2.
The BRCA2 defect they found, known as c.9976T, increased lung cancer risk from 15 per cent in non-smokers to 25 per cent. Effectively the mutation was found to double the relative risk of disease in smokers from around a 40-fold increased risk to closer to an 80-fold increased risk of developing lung cancer. This is said to be the strongest genetic association in lung cancer ever reported.
The researchers conclude that the study provides ’further evidence for inherited genetic susceptibility to lung cancer’. They note the potential public health implications ‘for identifying high-risk ever-smoking subjects for lung cancer screening’, and also suggest that PARP inhibitors, which have shown some success in breast and ovarian cancer treatment for people with BRCA2 mutations, may be effective for some cases of lung cancer, although further research is said to be needed.
Commenting on the findings, Cancer Research UK's chief clinician Prof Peter Johnson observed: “the single most effective way to reduce the risk of lung cancer is to be a non-smoker”.