Genes and environment : the official journal of the Japanese Environmental Mutagen Society
Gene-radon interaction effects on lung cancer risk: validation of susceptibility loci using archived DNA from German Uranium miners
By Rosenberger A, Bonzheim I, Fend F and 7 others.
Abstract
Background
Radon exposure increases lung cancer risk, shown in studies on indoor exposure (low exposure) and uranium miners (high exposure). Genome-wide and candidate gene studies have identified DNA variants that interact with occupational radon to modify lung cancer risk.
Method
Highly fragmented DNA samples of 611 individuals were genotyped using next-generation sequencing. DNA variant associations could be assessed in 526 out of 611 WISMUT uranium miners with lung cancer. The relative risk of lung cancer per allele (marginal effect) as well as its dependence on radon exposure (gene-environment (GxE) interaction) could be estimated from the enrichment of one allele compared to the distribution of genotypes expected under the HWE assumption (Hardy-Weinberg equilibrium). Exposure to gamma radiation, long-lived radionuclides, fine dust, silicate dust and arsenic was considered in the same way.