Tobacco smoke and ionizing radiation induce oxidative stress by transmitting or generating reactive oxygen species (ROS). We hypothesized that glutathione-S-transferase M1 (GSTM1) null homozygotes would have decreased ability to neutralize ROS that might increase their susceptibility to lung cancer. A case-only design was used with lung cancer cases pooled from three previously completed case-control studies using archival tissue samples from 270 lung cancer cases to genotype GSTM1. Radon concentrations were measured with long-term alpha-track radon detectors. Secondhand smoke was measured with questionnaires and interviews. Unconditional logistic regression was used to calculate the interaction odds ratios (OR) and 95% confidence intervals (95% CI). Radon concentrations > 121.26 Bq m-3 were associated with a > 3-fold interaction OR (OR = 3.41; 95% CI = 1.10, 10.61) for GSTM1 null homozygotes compared with GSTM1 carriers; the linear trend was significant (p trend = 0.03). The SHS and GSTM1 interaction OR was also elevated (OR = 2.47; 95% CI = 1.21-5.05) among never-smokers. This may be the first study to provide evidence of a GSTM1 and radon interaction in risk of lung cancer. Additionally, these findings support the hypothesis that radon and SHS promote neoplasia through shared elements of a common pathway.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]