2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38131Multiuple epidemiological studies have reported that a family history of breast can is a reproducible predictor of breast cancer risk. The reports have indicated that hereditary breast cancers are responsible for 4-10 % of breast carcinomas, among them most are developing early in tumor formation. BRCA-1and BRCA-2 are responsible for 90 % of the less frequent hereditary breast cancers. In sporadic breast cancers, P53mutations are responsible for 20-40 % of breast carcinomas. It was also reported that viruses were found in sporadic breast cancer tissues. Therefore, the correlation of viruses with breast cancers can not be excluded. Our previous study has syggested that the viruses associated with breast cancer were HHV-8>EBV (P < 0.01). Moreover, recent reports suggested that the Matrix Metalloproteinases 2 (MMP-2), IL-6, and IL-11 are associated with breast cancer. MMP-2 (72-kilodalton Type IV collagenase/gelatinase A)is a member of the multigene matrix metalloproteinases family, occurring in normal and malignant tissues. With the ability to degrade extracellular proteins it seems to play an important role in tumour cell invasion, metastasis, and angiogenesis. Several studies revealed a correlation between MMP-2 and breast cancer, showing that elevated MMP-2 expression reflects a more aggressive tumour and a poor prognosis: For example, Talvensaari-Mattila et al. (1998) found an association with MMP-2 immunoreactive protein and a shortened survival independent of major prognostic indicators in patients with primary breast carcinoma. The increased risk of death was 3.6-fold during the first 10 years of follow-up. Interleukin-6 (IL-6) and Interleukin-11 (IL-11) are pleiotropic cytokines, produced by many different cell-lines such as macrophages, T-cells, endothelial cells and tumour cells. They play an essential role in the acute phase reaction, in the hematopoesis, in the immune response and are additionally involved in the stimulation of osteoclast formation. IL-6 is also able to promote tumour growth by upregulating anti-apoptopic and angiogenic proteins in tumour cells. Moreover IL-6 and TNF-alpha can stimulate the activities of all the enzymes involved in estrogen synthesis in normal and malignant breast tissues. This fact seems to be of great importance, considering that most of the breast tumours are initially dependent upon estrogen to support their growth and that the concentration of estradiol, the biologically active estrogen, is higher in malignant that in normal breast tissues.Several studies showed a correlation between high levels of IL-6 in serum and poor prognosis in patients with prostate cancer, ovarian cancer, and indolent lymphoma and with a number of other malignant disorders. As mentioned above Il-11 and Il-6 are potent stimulators of osteoclast development. Therefore Sotiriou et al. examined their possible role as a predictive factor for further development of bone metastases. The results showed a significant correlation especially with IL-11 expression. To improve the accurate assessment for individual treatment of each patient and so to increase the disease free and overall survival, further investigation for helpful biomarkers is necessary.We hope that we can understand more about the breast cancer oncogenesis processes by the study of these serum markers involved in familial and non-familial breast cancer formation.家族史為乳癌危險因子中，再現性高的預測因子。遺傳性乳癌佔所有乳癌的4-10%，這些遺傳性 乳癌，大約有90%是經由BRCA-1 及BRCA-2 基因變異引起。在偶發性乳癌中以P53 變異佔約20-40%， 也有文獻指出在偶發性乳癌組織中發現有病毒的基因，而我們先前研究發現與乳癌相關的病毒為 HHV-8>EBV (P<0.01)， 因此本計畫第一部份將進一步進行其存活率預測與病毒感染因子的關聯性的 追蹤分析，這部份已在進行。而近年來關於乳癌的血清蛋白檢測，也有報導指出Matrix Metaloproteinase 2, IL-6, IL-11 等血清蛋白與乳癌有關。Matrix metalloproteinase-2 是蛋白.家族之一，可與細胞外基質 的降解有關，Metaloproteinase-2 的增加與多種腫瘤的變性增生有關。IL-6 與IL-11 是兩種多作用性 細胞激素，可由多種細胞產生，有研究也指出血清IL-6 的增加與Prostate cancer, Ovarian cancer, indolent lymphoma 等有關，而IL-11 與骨頭metastases 有關。我們先前的研究顯示非家族性乳癌與病毒感染相 關，這點與我們先前的子宮頸癌研究結果相似；而家族性乳癌與遺傳及其他非病毒感染因子相關，這 點與我們的口腔癌研究結果也相近，因此本計畫第二部份也將收集乳癌、子宮頸癌、口腔癌患者治療 前後血清，進行Metaloproteinase 2, IL-6 及IL-11 檢測與比較分析。我們預期研究的結果將對台灣地區 乳癌的發生提供必要的認識，這此認識不僅有助於我們解釋台灣乳癌發生的現況，也可能對診斷或治 療策略提供新的方向。病毒Matrix Metaloproteinase 2IL-6IL-11VirusMatrix Metaloproteinase 2IL-6IL-11Project