Gene variant linked to lung cancer risk

A variation of the gene NFKB1, called rs4648127, is associated with an estimated 44 percent reduction in lung cancer risk. When this information, derived from samples obtained as part of a large NCI-sponsored prevention clinical trial, was compared with data on a different sample collection from NCI’s genome-wide association studies (GWAS), lung cancer risk was still estimated to be lower, but only by 21 percent. While this variation of gene NFKB1 had not previously been linked to lung cancer risk, a protein produced by the NFKB1 gene has been associated with several important roles in immunity, inflammation, and cell proliferation. These findings, by Meredith Shiels, Ph.D., and Anil Chaturvedi, Ph.D., NCI Division of Cancer Epidemiology and Genetics, and their colleagues, were published October 8, 2012, in the journal Cancer.

In the samples derived from the prevention study, 1,429 variants in inflammation or immunity related genes were investigated. The investigators found a significant link between lung cancer and 81 single nucleotide polymorphisms (SNPs) located in 44 genes in innate immunity and inflammation pathways. SNPs are the most common type of changes in DNA. SNPs occur when a single nucleotide—a building block of DNA—is replaced with another of the 4 nucleotides (T,C,G or A) that comprise DNA.  The investigators then compared their results with data from four recently completed GWAS that included 5,739 lung cancer cases and 5,848 controls. Of the 81 SNPs identified, the rs4648127 SNP, which is located within the NFKB1 gene, was associated with lung cancer in both analyses. This association between the NFKB1 gene variant and lung cancer risk underscores the role of inflammation and immunity in lung cancer development, according to the investigators.