Lung cancer risk linked to dozens of gene variants

2019-03-02 05:05:00

By Roxanne Khamsi Sixty-four gene variants that may slightly predispose certain individuals to lung cancer have been revealed by the largest genetic survey into the disease to date. The discovery is step towards future tests aiming to identify those at high risk of developing the deadly condition. With diseases such as breast cancer, experts can easily point to at least a few genes known to significantly increase a person’s risk of developing the illness. But scientists had never struck upon any similarly key genes influencing lung cancer, which claims approximately 1.2 million lives worldwide each year. The new genome-wide survey, carried out by Richard Houlston of the Institute of Cancer Research, in Sutton, UK, and colleagues, has identified 64 DNA variants that seem to slightly increase a person’s risk of acquiring lung cancer. These variants are known as “low-penetrance alleles” because they only occasionally stimulate tumour development. This means they differ from the BRCA genes that significantly elevate a person’s risk of breast cancer, for example. Women who have inherited mutations in these genes face a lifetime risk of breast cancer as high as 80%, and an elevated risk of ovarian cancer. BRCA1 and BRCA2 mutations cause about 5% to 10% of all breast cancers among white women in the US, according to epidemiologists. But the effects of the newly discovered gene variants on lung cancer are more subtle. One variant might, for example, raise a non-smoker’s absolute risk of the disease by less than 1%, Houlston says. But these small increases may add up in an individual that has inherited many of the risk-carrying variants. To identify the genes, Houlston and colleagues analysed the DNA in blood samples collected from 1529 people with lung cancer and from 2707 individuals without the disease. In total, the team surveyed 871 genes among the volunteers, all of whom were white. Of the 64 gene variants they found, 11 are located within genes that encode key parts of a biological pathway involving insulin-like growth factor. Scientists developing future treatments for lung cancer may want to consider targeting this pathway, Houlston suggests. But he is keen to stress that the risk of lung cancer conferred by these genetic changes is minute compared to one particular lifestyle choice: “The fact is, the biggest risk factor for lung cancer is smoking.” Journal reference: Genome Research (DOI: