台灣乳癌病人COX-2基因多型性及其表現之研究

「乳癌」為歐美女性癌症的第一位，在國內為女性癌症罹患率之第二位，僅次於子宮頸癌，過去20年間呈現穩定的上升且逐年增加。雖然環境、基因、營養和荷爾蒙一般被認為與乳癌的形成有關，但是乳癌的發生學在現在仍未完全的被釐清。其發病的年齡台灣女性更較國外年輕10歲，平均年齡約48歲，預後較差且原因不明，故對於本土性之病因值得探討。由過去的文獻發現：長期的慢性發炎與癌症的罹患有密切的關係。例如：長期的慢性腸炎會導致罹患大腸癌的機率增加。最近幾年的流行病學研究指出： COX-2基因位於啟動區第-765位置的核?˙藻h型性似乎與多種癌症都有其相關性存在。在發炎與乳癌之間的關係尚未明朗之前，進行此研究。我們收集了134位病患以及150位健康女性的血液檢體進行實驗，運用限制?﹞軉q多型性分析法(Polymerase chain reaction - restriction fragment length polymorphism, 以下簡稱PCR-RFLP)，對乳癌病人COX-2基因-765G>C的多型性進行分析，並探討目前臨床上乳癌的臨床參數，例如：年齡、ER、PR、組織學分級(Histological grade)與COX-2 -765G>C基因多型性及其表現之間的相關性，希望藉此研究結果以做為臨床之應用參考。結果顯示：若以G/G基因型為基準，G/C基因型對比於G/G基因型之危險性為1.4倍（allele 1.3倍及表現型1.3倍），均未達統計上之顯著性差異。另外，若以45歲以前患病者定義為早發性乳癌，將受研究者分為兩群，再做探討。結果發現：45歲之前後，基因型、allele及表現型對於罹患乳癌的危險性，均不具有顯著性差異。因此我們的結論是攜帶C者，對於罹患乳癌的危險性並沒有顯著性差異。在COX-2的表現方面：若台灣地區的乳癌患者具有攜帶C者時，COX-2 mRNA過度表現的比例顯著較高，但是在COX-2蛋白質的表現方面則不具有顯著性差異。台灣地區的乳癌患者，HER2（陽性 V.S. 陰性）的COX-2蛋白質表現量，未達統計上之顯著性差異；但ER陽性或PR陽性者其腫瘤鄰近組織或腫瘤組織的COX-2蛋白質表現量都明顯高於陰性者，且具有統計學上的顯著性差異。有趣的是台灣地區的乳癌患者其COX-2蛋白質具有表現的比例明顯比國外婦女來的高（台灣70-80%，國外40-50%）。所以結論為：COX-2蛋白質高度表現的因素，或許是影響台灣乳癌年輕化且預後較差的主要原因之ㄧ。

關鍵字

乳癌；環氧化脢2基因多型性

並列摘要

Breast cancer has become one of the main cancers in Taiwan. The incidence rate of breast cancer has increased in last two decades. The etiology of breast cancer is still unknown, and environmental, genetic, nutritional and hormonal factors are known to contribute to the breast cancer risk. The Taiwanese women of suffering from rate of breast cancer are 10 years younger abroad, mean age is about 48 years old, have worse prognosis and reason clear, deserve the discussion to cause of disease, Taiwan of native country. A substantial body of evidence supports the conclusion that chronic inflammation can predispose an individual to cancer, as demonstrated by the association between chronic inflammatory bowel diseases and the increased risk of colon carcinoma. Several recent epidemiological studies demonstrated that there was a single missense point mutation at promoter -765 of COX-2 and this might be associated with various cancers. The relation between inflammation and breast cancer has not clear yet. We analyzed the genomic DNA -765G>C of COX-2 polymorphism with a PCR-RFLP assay in 134 patients with breast cancer and 150 controls. In addition, we also evaluated the relationships of the COX-2 genotype to the COX-2 protein expression, age, hormone receptors (ER, PR), and histological grades in patients with breast cancer. The results showed that the odds ratio of the G/G and G/C genotype were 1.4.(allele were 1.3, phenotype were 1.3.) However, there was no significant difference in the polymorphism of COX-2 in the case-control study. The patients were classified into two groups according to the patients defined as an early-onset breast cancer (by 45 years of age). After analysis, we found that patients who were over 45 years of age had a higher odds ratio of the G/C genotype compared with those of younger than 45 years of age (2.41 vs. 0.85). There was no significantly. We conclude that the C carrier genotype could’t plays a strong role in breast cancer. There was significantly higher the expression of COX-2 mRNA in the patients with G/C genotype than that of G/G genotype. There were no correlations between the -765 G>C of COX-2 genotype and either of COX-2 and hormone receptor protein status and MnSOD polymorphism and tumor sizes and histological grades in patients with breast cancer. There were correlations between the expression of COX-2 protein and either of ER positive and PR positive was significantly higher than ER negative and PR negative. The expression of COX-2 protein of patients with breast cancer in Taiwan was higher proportion than foreign. This means that the occurrence of breast cancer may induce the expression of COX-2 protein. The mechanism is unknown, and there will be more studies to confirm it. We conclude that overexpression of COX-2 protein maybe a role in Taiwan’s patients with breast cancer who are 10 years younger than abroad and have worse prognosis.

並列關鍵字

Breast cancer ； Cyclooxygenase-2

參考文獻

References

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