| Summary: | 碩士 === 國立中興大學 === 環境工程學系所 === 101 === The objectives of this research were to investigate the associations of the risk factors of breast cancer, including body mass index (BMI, Kg/m2) , age, and polymorphisms of genes involved in DNA repair and estrogen metabolism with the background levels of abasic sites (AP sites) in Taiwanese women with breast cancer and controls. Results indicated that the background levels of AP sites (mean ± SD) in healthy controls (n=140) were estimated to be 23.3 ± 13.5 per 106 nucleotides. There is a 2.2-fold increase in the background levels of AP sites when compared to our previous finding in breast cancer patients (50.3± 59.2 per 106 nucleotides) (p<0.001). The AP sites found in both controls and breast cancer patients were primarily derived from oxidative stress (~60%) as assayed by Putrescine-cleavage assay. Further investigation indicated that among subjects with age under 50, the number of AP sites detected in breast cancer patients was about 2.7-fold greater than that in controls. Similarly, levels of AP sites were about 2.4-fold greater in breast cancer patients than in controls among subjects with BMI<27 or with variant alleles of DNA repair genes APE1 Asp148Glu (p<0.001). This evidence suggests that circumstances associate with subjects status, including age under 50, BMI<27, and variant alleles of APE1 Asp148Glu, further enhance the levels of AP sites in breast cancer patients.
Results from SNP analysis indicated that the frequencies of variant alleles of DNA repair genes APE1 Asp148Glu were estimated to be 46.2% and 46.3% (p>0.05) for controls and breast cancer patients, respectively, whereas bioactivation genes (NQO1 C609T) were estimated to be 45.5% and 42.4% (p>0.05) for controls and breast cancer patients, respectively. These findings strongly suggest that variant alleles of APE1 Asp148Glu and NQO1 C609T do not associate with the risk of developing breast cancer in Taiwanese women. However, we did observe the background levels of AP sites in controls with homozygous variant alleles (Glu/Glu) were about 1.3-fold greater than those with wild-type (Asp/Asp) whereas a 2.08-fold increase was found in breast cancer patients. This evidence infer that there is a significant decrease in repair efficiency of variant alleles of APE1 Asp148Glu, may further lead to the subsequent accumulation of AP sites in living cells.
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