Investigation of the Association of Genetic Polymorphisms in DNA Repair Genes and the Background Levels of Abasic sites with the Risk of Developing Breast Cancer in Taiwanese women

• Main Authors: Jhen-Han Wang, 王貞涵
• Other Authors: Po-Hsiung Lin
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/01449618291067575281

碩士 === 國立中興大學 === 環境工程學系所 === 102 === The objectives of this research were to investigate the associations of the risk factors of breast cancer, including polymorphisms of genes involved in DNA repair, e.g. X-ray repair cross-complementing protein 1(XRCC1) and Poly [ADP-ribose] polymerase 1(PARP-1), with the background levels of abasic sites (AP sites) in Taiwanese women with breast cancer and controls. Additionally, we examined the effects of environmental carcinogens, including tobacco carcinogens(4-(methylnitro-samino)-1-(3-pyridyl)-1-butanone, NNK) anddioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) on the induction of DNA single strand breaks by 17β-estradiol (E 2 ) in human MCF-7breast cells. Results from the first part of this study indicated that the frequencies of variant alleles of DNA repair genes XRCC1 R399Q were estimated to be 33.2% and 38.4% for controls and breast cancer patients, respectively, whereas DNA repair genes PARP1 V762A were estimated to be 59.4% and 57.4% for controls and breast cancer patients, respectively.These findings suggest that variant alleles of XRCC1 R399Q and PARP1 V762A do not associate with the risk of developing breast cancer in Taiwanese women. Results from the second part of this research using the single-cell gel electrophoresis assay confirmed that E 2 and NNK alone did not induce significant increases in the number of DNA strand breaks in MCF-7 cellswhereas significant increases in the number of DNA strand breaks were detected in cells treated with TCDD when compared to control (~8 fold). Co-treatment of E 2 and TCDD further enhance the induction of DNA damage in cells (~24 fold). Similarly, in the presence of NNK, E 2 induced significant increases in the number of DNA strand breaks (~8 fold). By contrast, the extent of DNA lesions were dramatically reduced in cells treated with NNK, TCDD, and E 2 when compared to control (~4-fold). Overall, this evidence strongly suggests the presence of antagonistic effect of among these three compounds on the formation of DNA lesions in MCF-7 cells.