E-cadherin 基因之promoter 區域(-160 C→A)多型性與大腸 直腸癌致癌危險性的關係

Abstract

曾有報告指出E-cadherin 的promoter region 之-160℃→A 的基因多型性會增 減E-cadherin 基因的表現性。因此，評估E-cadherin 基因表現的多型性或許可以 鑑定出那些人具有罹患大腸直腸癌的危險性。然而，至今此類的報告卻只有零星 數篇而已。本研究是依個以台大醫院病例為基礎之病例控制性分析研究，我們共 收集了200 位大腸直腸癌病患與200 正常人。DNA 標本取自病患周邊血液白血 球，經聚合酶鏈鎖反應放大欲檢驗之DNA 片段，然後以限制酶切割分析基因多 型性。我們以回歸分析統計學計算此基因多型性的危險係數及95%信賴區間。並 經過統計調整其飲食生活習慣等因素（如嗜食紅肉、抽菸、喝酒、肥胖、糖尿病） 的影響。我們發現在200 位健康台灣人中，E-cadherin 基因型的分布是CC 佔42% （n=84），C/A 占48.0%（n=96），而AA 占10%（n=20）。而在大腸直腸癌病患 中AA 基因型的頻率（2%，n= 4 of 200）統計學上明顯比控制組的健康成人低 （p<0.005），其罹患大腸直腸癌的危險性約只有CC 基因型者的五分之ㄧ （OR=0.20；95% CI=0.06-0.56）。將這些大腸直腸癌患者依照病灶位置（左側vs. 右側大腸），組織學型態（分化良好、中度、以及不良），腫瘤期別（stage 0、Ⅰ 對stageⅡ、Ⅲ、Ⅳ期），以及淋巴腺轉移（陽性對陰性）等因子與E-cadherin 的 關聯分析中，並未發現任何相關。我們的結論E-cadherin-160A/A 基因型會降低 大腸直腸癌罹病的危險性。接下來必須探討A 型態的基因型到底在腫瘤組織中對 E-cadherin 功能所產生的影響，以及收集更多的病例，以進一步確定相關性。

A 160℃→A polymorphism in the promoter region of E-cadherin has been reported to decrease gene transcription. This allelic variation might be a potential genetic marker for identifying individuals at risk for colorectal cancer. Up to date, only very few reports were published the regarding clarification of the association between the polymorphism of E-cadherim and colorectal cancer. A hospital-based case-control study, including 200 colorectal cancer patients and 200 unaffected controls, was performed. DNA from peripheral blood samples was examined by polymerase chain reaction-restriction fragment length polymorphism. Logistic regression analyses were used to computed odds ratio (OR) and 95% confidence interval (CI) after adjusted for the influence from diet and life-style factors (e.g. red meat, smoking, drinking, obesity, and diabetes mellitus ). In 200 healthy Taiwanese, the distribution of genotype C/C was 42% (n=84), C/A was 48.0% (n=96), and AA was 10% (n=20). The frequency of variant A/A genotype in colorectal cancer cases (4 of 200, 2%) was significantly lower than that of controls (20 of 200, 10%) (p<0.005), conferring a 5-hold decrease in the risk of colorectal cancer (OR, 0.20 : 95% CI, 0.06-0.56) compared with the C/C genotype. Stratification of the colorectal cancer cases according to their location (left-sided vs. right-sided colon), histology (well, moderate, and poor differentiation), tumor stage (stage 0, Ⅰvs. stageⅡ,Ⅲ,Ⅳ), and lymph node metastasis(positive and negative) fail to reveal any heterogeneity with resped to E-cadherin genotype. The present data suggest that individuals with E-cadherin-160 A/A genotype have a decreased risk of colorectal cancer. Further study is mandatory to clarify the functional relevance of the A allele in vivo and to confirm the inverse association of the A/A genotype with colorectal cancer in large epidemiologic studies.