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| 題名: | DNA錯誤配對辨識蛋白2、3、6基因多形性與乳癌之相關性研究
Association of Genetic Polymorphisms of MutS Homolog 2, 3, 6 with Breast Cancer |
| 作者: | 莊晴雲
Chuang, Ching-Wen |
| 貢獻者: | 邱弘毅 |
| 關鍵詞: | 乳癌,錯誤配對修復(MMR),MutS基因多形性,基因多形
Breast cancer,Mismatch repair (MMR),Genetic polymorphisms of MutS genes |
| 日期: | 2013-06-14 |
| 上傳時間: | 2018-09-27 16:07:47 (UTC+8) |
| 摘要: | 乳癌在全世界婦女中是最常見的惡性腫瘤疾病。臺灣近十幾年來乳癌標準化發生率於婦女惡性腫瘤發生率皆位居第一位，顯示乳癌是一個很重要的公共衛生議題。錯誤配對修復系統(Mismatch Repair System, MMR)主要功能是消除DNA在複製過程中所產生的錯誤配對以及插入/缺失之環狀結構。MMR基因主要由錯誤配對辨認蛋白MutS、錯誤配對修補蛋白MutL組成。當錯誤配對修復(MMR)失去功能，會導致高突變率、微衛星不穩定(MSI)、異型合子的缺失(LOH)、造成抗細胞凋亡、增加致癌的易感性。因此，本研究目的為針對MMR當中MutS基因，探討MSH2 rs2303425、MSH3 rs26279及MSH6 rs2020910基因多形性與危險因子對乳癌的獨立與交互作用。
本研究對象包括來自北醫、萬芳、雙和、國泰四間醫療院所的598位乳癌病患與598位經年齡頻率配對的對照健康族群。資料收集為利用結構式問卷且標準化流程收集基本人口學、相關危險因子等。基因多形性之判定是利用聚合連鎖反應(Polymerase chain reaction, PCR)、限制片段長度多形性(Restriction fragment length polymorphism, RFLP)與對照兩組引子的聚合連鎖反應(Polymerase chain reaction with confronting two-pair primers, PCR-CTPP)。統計方法使用t檢定及卡方檢定比較病例及對照的差異，並且使用邏輯斯迴歸分析MutS基因多形性和危險因子對乳癌之相關性。
研究結果顯示停經年齡晚、未停經及曾抽菸者會增加罹患乳癌之風險。基因多形性分析發現，調整年齡、停經狀態、抽菸狀況及乳癌家族史後，MSH2 rs2303425基因多形性攜帶C對偶基因相較於TT基因型者有1.3倍罹患乳癌的風險。停經年齡50歲、未停經以及曾抽菸者若攜帶MSH2 rs2303425、MSH3 rs26279或MSH6 rs2020910危險基因型具有顯著較高罹患乳癌之風險，且具有顯著劑量效應關係。另外，停經年齡50歲與不同MutS基因多形性組合的危險基因型數目之交互作用下皆有顯著較高罹患乳癌的風險，並且具有劑量效應關係。
總結以上，本篇研究發現MSH2 rs2303425基因多形性與乳癌風險有相關性。另外，停經年齡晚、未停經者或曾抽菸者，同時攜帶MSH2 rs2303425、MSH3 rs26279或MSH6 rs2020910危險基因型有較高罹患乳癌之風險。
Breast cancer is the most common female malignant tumors of the world. Breast cancer had the highest age-standardized incidence rate than any other cancer sites among females in Taiwan in the past ten years, showing breast cancer is a very important issue of public health. DNA mismatch repair (MMR) plays an important role to eliminate mismatches and insertion-deletion loops during DNA replication. The MMR system is comprised of MutS and MutL families. The failure of MMR functions leads to high mutation rates, MSI, LOH, reduction in apoptosis processes and predisposition for carcinogenesis. Therefore, this study evaluated the association between breast cancer risk and 3 genetic polymorphisms of MutS genes in MMR genes.
598 breast cancer patients from TMU, Wan-Fang, Shuang-Ho and Cathay General Hospitals in Taiwan and 598 healthy controls were frequency matched by age. All subjects were interviewed by well-trained research assistants that using standardized questionnaire to collect information on demographic characteristics and breast cancer risk factors. We genotyped three genetic polymorphisms by using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction with confronting two-pair primers (PCR-CTPP) methods. Student t test and Chi-Square (X2) test were used to compare differences between cases and control. Logistic regression was used to assess the association between genetic polymorphisms of MutS genes and breast cancer.
Our study showed that menopause with late age, premenopausal and ever smoked were associated with an increasing risk of breast cancer. After adjusted for age, menopausal status, smoking status and family history of breast cancer, the risk from variant-containing genotypes (TC+CC) of MSH2 rs2303425 had 1.3-fold significantly increased risk (95% C.I.:1.00-1.68) when compared with homozygous wild-type TT genotype. High risk genotypes of MSH2 rs2303425, MSH3 rs26279 and MSH6 rs2020910 among those with late menopause, premenopausal and ever smoked were associated with increasing risk of breast cancer, showing a significant trend. Moreover, signicant trend in associating late menopause with different combinations of high risk genotypes for MSH2 rs2303425, MSH3 rs26279 and MSH6 rs2020910 were also found.
In summary, our current data suggest that MSH2 rs2303425 was associated with the risk of breast cancer. Study subjects with menopause with late age, premenopausal or ever smoked and also with high risk genotypes of MSH2 rs2303425, MSH3 rs26279 or MSH6 rs2020910 were affected with increasing risk of breast cancer. |
| 描述: | 碩士
委員-沈志陽
委員-謝芳宜
指導教授-邱弘毅 |
| 資料類型: | thesis |
| 顯示於類別: | [公共衛生學系暨研究所] 碩博論文
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