Epidemiology and Biostatistics
BACKGROUND: Polycyclic aromatic hydrocarbon (PAHs) may increase breast cancer risk, and the association may be modified by inherited differences in deactivation of PAH intermediates by glutathione S-transferases (GSTs). Few breast cancer studies have investigated the joint effects of multiple GSTs and a PAH biomarker.
OBJECTIVE: We estimated the breast cancer risk associated with multiple polymorphisms in the GST gene (GSTA1, GSTM1, GSTP1, and GSTT1) and the interaction with PAH-DNA adducts and cigarette smoke.
METHODS: We conducted unconditional logistic regression using data from a population-based sample of women (cases/controls, respectively): GST polymorphisms were genotyped using polymerase chain reaction and matrix-assisted laser desorption/ionization time-of-flight assays (n = 926 of 916), PAH-DNA adduct blood levels were measured by competitive enzyme-linked immunosorbent assay (n = 873 of 941), and smoking status was assessed by in-person questionnaires (n = 943 of 973).
RESULTS: Odds ratios for joint effects on breast cancer risk among women with at least three variant alleles were 1.56 [95% confidence interval (CI), 1.13-2.16] for detectable PAH-DNA adducts and 0.93 (95% CI, 0.56-1.56) for no detectable adducts; corresponding odds ratios for three or more variants were 1.18 (95% CI, 0.82-1.69) for ever smokers and 1.44 (95% CI, 0.97-2.14) for never smokers. Neither interaction was statistically significant (p = 0.43 and 0.62, respectively).
CONCLUSION: We found little statistical evidence that PAHs interacted with GSTT1, GSTM1, GSTP1, and GSTA1 polymorphisms to further increase breast cancer risk.
Published in Environmental Health Perspectives, Volume 117, Issue 4, 2009, pages 552-558.
McCarty, K. M., Santella, R. M., Steck, S. E., Cleveland, R. J., Ahn, J., Ambrosone, C. B., ... Gammon, M. D. (2009). PAH-DNA adducts, cigarette smoking, GST polymorphisms, and breast cancer risk. Environmental Health Perspectives, 117(4), 552-558.
Reproduced with permission from Environmental Health Perspectives
© Environmental Health Perspectives, 2009, National Institute of Environmental Health Sciences