| 摘要: | 癌症是台灣地區近年來十大死亡原因的連續榜首,而乳癌卻是台灣女性發生比例最高的癌症，台灣每天有5名台灣婦女因乳癌而死亡,有16-18名台灣婦女被診斷出乳癌, 乳腺癌是台灣公眾健康的一個重要問題，它已躋身影響健康的台灣女性最常見的癌症之一。為了要了解乳腺癌發展的分子機制，研究人員採用了候選基因/機制戰略，以確定假定的致瘤基因和途徑，然後用分子流行病學研究和體外/體內實驗來審視乳癌發生的真正原因。而這些候選基因主要涉及維持基因組的穩定性，修復DNA損傷，調節細胞週期和滅活雌激素的致癌代謝物。分子流行病學研究則透通過探討乳腺癌女性患者與健康女性間，其基因型多態性可能存在的差異性，並利用在體外/體內實驗來確定乳腺癌易感基因之間的分子相互作用。
最近， 全基因組研究分析(GWAS)可以幫助我們指出影響癌症形成的重要性SNP因此我們嘗試使用GWAS方法來尋找一些與乳腺癌發生和復發(或死亡)的關聯基因座。我們收集889名乳腺癌患者在台灣女性的血液樣本，提取DNA ，並進行了基因晶片分析：包括19萬點位（劍橋大學英格蘭Icogs ）。
在GWAS 分析中，比較在沒有帶有ER 染色的病人中，其乳癌的發生與復發族群間，我們發現有四個位點與病患的生存有顯著性的相關：包括rs7521422（ 1號染色體） ， rs12135374 （ 1號染色體）， rs2642978 (8號染色體)和c8_pos128477243（線粒體）。從生物信息學的研究，這些位點分別位於與腫瘤發育相關的幾個轉錄因子基因上，包括ZNF670 ， ZNF 695和POU5F1P1。
總結，我們的結果發現，有些參與癌症發展的幾個轉錄因子與乳腺癌患者的生存率有關。這些結果不僅讓我們知道乳腺癌的發展，同時也可能提供新的癌症防治戰略和新的治療和診斷方法。
Cancer is the head of top ten factor of death in Taiwan during the recent years and the breast cancer is the highest proportion in Taiwanese women. There are five women who die of breast cancer and 16-18 Taiwanese women are diagnosed to breast cancer every day in Taiwan. Breast cancer is an importance issue of public health in Taiwan, and it has ranked one of the most common cancers affecting health for Taiwanese women. To understand molecular mechanisms underlying breast cancer development, researchers have adopted the candidate genes/mechanisms strategy to identify putative tumorigenic genes and pathways, and then applies both molecular epidemiological study and in vitro/in vivo experiments to examine their breast tumorigenic contribution. These genes are mainly involved in maintaining genomic stability, repairing DNA damages, regulating cell cycle and inactivating carcinogenic estrogen metabolites. Molecular epidemiological study is conducted by exploring possible differences of genotypic polymorphisms between breast cancer women patients and healthy women, and in vitro/in vivo experiments aim at defining molecular interactions between breast cancer susceptibility genes.
Recent, GWAS could help us to point out the importance SNPs that affect the cancer formation and we try to use GWAS method to identify the association loci with breast cancer between occurrence and reoccurrence (some died).
The blood sample of 889 breast cancer patients in Taiwanese women were collected, extracted for DNA, and performed the gene chip analysis: including 190 thousand Loci (Cambridge University England Icogs). In GWAS, there were four loci: included rs7521422 (chromosome 1), rs12135374 (chromosome 1), rs2642978 (chromosome 8) and c8_pos128477243 (mitochondria) significant associated with patient’s survival in subjects without ER. From the bioinformation, these loci were located in several transcription factors including ZNF670, ZNF 695 and POU5F1P1, which involved in cancer development.
In conclusion, our founding was shown that several transcription factors involved in cancer development were associated with survival of breast cancer subjects. Those results would not only yield crucial insight to know how breast cancer develops, but they might also result in new cancer prevention strategy and new therapeutic and diagnostic approaches. |
