Radon, Tobacco Exposure and Non-Small Cell Lung Cancer Risk Related to BER and NER Genetic Polymorphisms

Tobacco consumption and radon exposure are considered the first and second most common causes of lung cancer, respectively. The aim of this study was to analyze both whether selected genetic polymorphisms in loci that are in DNA repair pathways, are related to non-small-cell lung cancer (NSCLC) and whether they may modulate the association between residential radon exposure and lung cancer in both smokers and never smokers.

A multicentre, hospital-based, case-control study with 826 cases and 1201 controls was designed in a radon-prone area. Genotyping was determined in whole blood and residential radon exposure was measured in participants' dwellings.

Attending to tobacco exposure, the variant in the gene NBN (rs1805794) was associated with lung cancer in never smokers (OR 2.72; 95%1.44-5.2) and heavy smokers (OR 3.04; 95%CI 1.21-7.69). The polymorphism with the highest lung cancer association was OGG1 (rs125701), showing an OR of 8.04 (95%CI 1.64-58.29) for its homozygous variant genotype in heavy smokers. Attending to indoor radon exposure (>200Bq/m³), rs1452584, for its homozygous variant genotype, showed the highest association (OR 3.04 (95%CI 1.15-8.48).

The genes analyzed seem to have no association with the fully adjusted model, but they might modulate lung cancer association when different categories of tobacco consumption are considered (i.e. heavy smokers). This association may similarly be elevated for those individuals having high indoor radon exposures, though at a minor extent.