Breast Cancer Risk is Associated with The Genes Encoding the DNA Double-Strand-Break Repair Mre11/Rad50/Nbs1 Complex

• Main Authors: Huan-Ming Hsu, 許桓銘
• Other Authors: Chern-Yang Shen
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/75873010948046106509

博士 === 國防醫學院 === 醫學科學研究所 === 96 === Breast cancer is one of the most common female cancers in Taiwan; the incidence and mortality of breast cancer have been increasing over the past two decades. The pathogenesis of breast cancer is the important issue for study. The risk factors about breast cancer include early menarche, late menopause and nulliparity. These results infer exposure of estrogen associated with breast tumorignesis. Many evidences support estrogen induces cell proliferation to oncogenesis of mammary cells. And the metabolites of estrogen is also endogeneous oncogenic agent to DNA double-strand break. DNA double-strand break is a fateful event to cells. The function of DNA double-strand break repair system is critical to maintain genomic stability of cells. The Mre11/Rad50/Nbs1 complex plays an important role for repair system. We proposed the hypomorphic variants of these three genes are associated with breast cancer risk. In this study, we collected 559 female breast cancer patients and 1125 female healthy control. Genotyping of Mre11, Rad50 and Nbs1 were performed for this case-control study. All patient and controls completed the designed questionnaire. Biostatic analysis was done for collected data. These results display Nbs1 polymorphic variant is significantly associated with breast cancer risk. Because the Mre11/Rad50/Nbs1 is an complex protein, the function becomes decreased if any defect of these three proteins. The polymorphic variants of three genes have joint effect to breast cancer risk. And the exposure of estrogen increases the breast caner of high risk genotypes. The MRE11 protein has interaction with the BRCA1 protein while DNA double-strand break in vivo. These findings support the hypothesis that defect of DNA repair genes Mre11, Rad50 and Nbs1 are associated with breast tumorigenesis.