Abstract
We aimed at determining whether any association exists between genetic polymorphisms in epoxide hydrolase (EPHX1), NADPH-quinone oxidoreductase (NQO1), glutathione S-transferases (GSTM1/P1/T1) and individual susceptibility to breast cancer. Polymerase chain reaction-restriction fragment length polymorphism-based genotyping assays were used to determine the frequency of polymorphisms in EPHX1 (exons 3 and 4), NQO1 (exon 6), GSTM1 (deletion), GSTP1 (exon 5), and GSTT1 (deletion) in a case–control study comprised of 238 patients with breast cancer and 313 healthy individuals. The distribution of genotypes in exon 6 of NQO1 was significantly different between the control group and breast cancer cases. Age-adjusted odds ratio (OR) for variant genotype NQO1*2/*2 was 3.68 (confidence interval (CI)=1.41–9.62, P=0.008). Association of GSTP1*2/*2 genotype as well as that of low EPHX1 activity deduced by combinations of genotypes in exons 3 and 4 with breast cancer was suggestive, but nonsignificant. Individuals simultaneously lacking GSTM1 and carrying at least one GSTP1 variant allele were at significantly higher risk of breast cancer (OR=2.03, CI=1.18–3.50, P=0.010). Combinations of either GSTM1null or GSTP1*2 with low activity of EPHX1 presented significant risk of breast cancer (OR=1.88, CI=1.00–3.52, P=0.049 and OR=2.40, CI=1.15–5.00, P=0.019, respectively) as well. In conclusion, the results suggest that genetic polymorphisms in biotransformation enzymes may play a significant role in the development of breast cancer.
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Acknowledgements
We express our sincere thanks to doctors and nurses of Teaching Hospitals in Praha and to all patients and recruited control subjects for their essential help and understanding. Jana Sarmanova was partly supported by stipend of the third Medical Faculty of the Charles University in Prague, Czech Republic. The work at this project was supported by grant of Grant Agency of the Czech Republic, Grant No.: 310/01/1537.
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Šarmanová, J., Šůsová, S., Gut, I. et al. Breast cancer: role of polymorphisms in biotransformation enzymes. Eur J Hum Genet 12, 848–854 (2004). https://doi.org/10.1038/sj.ejhg.5201249
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DOI: https://doi.org/10.1038/sj.ejhg.5201249
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