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Environ Health Perspect. 2009 Apr;117(4):552-8. doi: 10.1289/ehp.0800119. Epub 2008 Dec 10.

PAH-DNA adducts, cigarette smoking, GST polymorphisms, and breast cancer risk.

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  • 1Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. kathleen.mccarty@yale.edu

Abstract

BACKGROUND:

Polycyclic aromatic hydrocarbons (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 smoking.

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.

KEYWORDS:

GST; Long Island; PAH-DNA adducts; breast cancer; smoking

PMID:
19440493
[PubMed - indexed for MEDLINE]
PMCID:
PMC2679598
Free PMC Article
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