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Background: The quinone oxidoreductases, NAD(P)H:quinone oxidoreductase 1 (NQO1) and NRH(dihydronicotinamide riboside):quinone oxidoreductase 2 (NQO2), are integral flavoproteins responsible for the detoxification and metabolism of quinones and quinoid compounds. NQO1 and NQO2 protect cells against accumulation of toxic quinoid compounds, as well as against mutagenicity and carcinogenicity. The aim of this study was to assess the importance of gene expression of NQO1 and NQO2 and breast cancer development and/or progression in line with known frequent polymorphisms. We focused on the NQO1 polymorphism causing exchange of Proline to Serine at position 187 which leading to a nonfunctional enzyme. In NQO2, rarely studied insertion/deletion in promotor and Phe47Leu exchange in exon 3 were addressed.

Materials and Methods: Levels of NQO1 and NQO2 mRNAs were monitored in human carcinomas of the mammary gland, mammary tissue without presence of tumor cells and in peripheral blood lymphocytes. Real-time PCR using absolute quantification and normalization to the expression of control gene cyclophilin A was used. Polymorphisms in NQO1 and NQO2 were assessed in DNA samples from peripheral blood lymphocytes of the same patients by PCR-RFLP based methods and DNA sequencing.

Results: Polymorphism in NQO1 was associated with increased risk of breast cancer in Czech population. Moreover, we observed high interindividual variability in NQO1 and NQO2 expression among patients and differences between tumor and non-tumor tissues. Different expression patterns in samples divided according to the presence of genetic polymorphisms in NQO1 and NQO2 were observed as well. By comparing these data with result of primary adjuvant therapy the clinical significance of NQO1 and NQO2 expression and genetic variability seems to be evident.

Conclusions: First study on genetic profiles of NQO1 and NQO2 in Czech breast cancer patients suggested that variations may play a role in the development and progression of breast cancer. Multiplex analysis of NQO1 and NQO2 polymorphism and expressions on larger and multiethnic cohorts should refine possible use in prediction and modification of breast cancer therapy.

This study was supported by grants of Internal Grant Agency of Ministry of Health of the Czech Republic, no.: 1A/8248, and 8563-5.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

American Association for Cancer Research
2007