Increased formation of oxidative DNA damage, 8-hydroxy-2 '-deoxyguanosine,in human breast cancer tissue and its relationship to GSTP1 and COMT genotypes

Reactive oxygen species (ROS) induced damage to DNA plays a major role in c arcinogenesis. Tn order to estimate the level of oxidative damage and its r ole in breast cancer, 8-hydroxy-2'-deoxyguanosine (8-OHdG) was determined i n DNA isolated from human breast tissue. Furthermore, we investigated wheth er polymorphisms in genes for enzymes involved in generation and eliminatio n of ROS had any association with the level of 8-OHdG in breast tissue. In this study, the level of 8-OHdG in DNA was measured by the high performance liquid chromatography-electrochemical detector (HPLC-ECD) method. Genotype s of cytochrome P450 (CYP)1A1, glutathione S-transferase (GST)M1, GSTP1 and catechol O-methyltransferase (COMT) were determined by PCR-based restricti on fragment length polymorphism analysis. A total of 61 Japanese patients w ere included in the study. The mean level of 8-OHdG in DNA of breast cancer tissues was 2.07 +/- 0.95 per 10(5) dG residues, while the mean level of 8 -OHdG in DNA of non-cancerous breast tissues was 1.34 +/- 0.46 per 10(5) dG residues. The 8-OHdG levels in DNA of breast cancer tissues were significa ntly higher than those of their corresponding non-cancerous breast tissues (P < 0.0001). There was negative correlation between the clinical stage and the mean level of 8-OHdG in DNA of breast cancer tissues. Furthermore, pat ients with genotype of high GSTP1 activity had lower level of 8-OHdG in DNA of breast cancer tissues than others. On the contrary, the mean level of 8 -OHdG in DNA of breast cancer tissues was higher among patients with genoty pe of high COMT activity. Our findings support the assumption that cancer c ells are more exposed to oxidative stress than adjacent non-cancerous tissu e. Genetic polymorphisms in enzymes involved in ROS metabolism may have a r ole in individual susceptibility to oxidant-related breast disease. At the same time, reduction of oxidative stress is thought to be a very important measure for primary prevention of breast cancer. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.