Abstract
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 3 previously completed case‐control studies using archival tissue samples from 270 lung cancer cases to genotype GSTM1. Radon concentrations were measured with long‐term α‐track radon detectors. Secondhand smoke (SHS) 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 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 to GSTM1 carriers; the linear trend was significant (p trend = 0.03). The SHS and GSTM1 interaction OR was also elevated (OR = 2.28; 95% CI = 1.15–4.51) 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. © 2006 Wiley‐Liss, Inc.