Radon, secondhand smoke, glutathione-S-transferase M1 and lung cancer among women.
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 alpha-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.
Bonner
Matthew R
MR
Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Rockville, MD, USA. mrbonner@buffalo.edu
Bennett
William P
WP
Xiong
Wenying
W
Lan
Qing
Q
Brownson
Ross C
RC
Harris
Curtis C
CC
Field
R William
RW
Lubin
Jay H
JH
Alavanja
Michael C R
MC
D000368:Aged; D004781:Environmental Exposure; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011886:Radon / Q000009:adverse effects*; D012107:Research Design; D012307:Risk Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D005982:Glutathione Transferase; D011886:Radon; D014028:Tobacco Smoke Pollution