貝他型腫瘤壞死因子NcoI基因多樣性與大腸癌的關聯性

The association of tumor necrosis factor beta-NcoI polymorphism with colorectal cancer

黃彩雲(Tsai-Yun Huang)

指導教授 ： 許立松

中山醫學大學/醫學院/生化暨生物科技研究所/碩士(2013年)

https://doi.org/10.6834/CSMU.2013.00127

摘要

大腸直腸癌是全世界第三個最常見的癌症，在台灣地區的罹患率
也高居第二位，而其癌症死亡率居第三位。過去的文獻已經提出相關的危險因子包括年齡的增加、性別（男性較易罹患大腸直腸癌）、發炎性腸道疾病、某些遺傳性條件和大腸直腸癌的家族史，都可能是導致大腸直腸癌的發生。有許多研究證實，單一核苷酸多型性與某些癌症和疾病的產生是有關聯性的。腫瘤壞死因子 (TNF) 是一種能直接造成腫瘤細胞死亡的細胞激素，它可啟動控制細胞增殖和凋亡的信號，以防止細胞炎症、自體免疫疾病或惡性腫瘤的發病過程。而 TNF-β 則是屬於腫瘤壞死因子家族的一員，當淋巴球被刺激產生分泌型 LTα (TNF-β) 後，它與 TNFR1 或 TNFR2 結合，引發細胞凋亡或活化典型 nuclear factor kappa-B (NFκB) 路徑造成發炎基因表現或淋巴再生，目前經許多研究都證實這個 TNF-β 的基因多型性與各種惡性疾病的發生是有關的。因此，本次實驗是針對TNF-β基因多型性與大腸直腸癌之間的相關性進行探討。利用聚合酶連鎖反應-限制酶切割片段長度多型性分析55位大腸癌患者其TNF-β多型性之等位基因的頻率，接著再與134位健康的對照組（IIA，無任何病史者，N = 58；IIB，具有傳統心血管疾病危險因子的病患，N = 76）進行統計分析。實驗結果顯示TNF-β genotype 之 G/G 同型合子與 genotype AG+AA 在實驗組 Group CRC 與對照組 Group ⅡA (無任何病史) 之間的結果具有顯著性的差異 (P 值 = 0.035)。我們的研究是首先提出在台灣地區的人群中 TNF-β NcoI 基因多型性與大腸直腸癌的發生是有關聯性的。

關鍵字

貝他型腫瘤壞死因子 ； 基因多樣性 ； 大腸癌

並列摘要

Colorectal cancer represents the third most common cancer
worldwide, and also the second highest prevalence, and its ranks third in cancer mortality in Taiwan region. It has been proposed that risk factors for colorectal cancer include increased age, gender (men are more predisposed to the development of colorectal cancer), the presence of inflammatory bowel disease, certain hereditary conditions and a family history of colorectal cancer. There are many studies indicated that single nucleotide polymorphism (SNPs) are associated with some cancers and diseases. Tumor necrosis factor (TNF) is a kind of cytokine which cause tumor cell death directly. It can initiate signals for cell proliferation and apoptosis (programmed cell death) to prevent inflammation, autoimmune diseases or cancer pathogenesis. TNF-β belongs to the TNF superfamily. When lymphocytes are stimulated to produce secretory LTα (TNF-β), it can interact with TNFR1 or TNFR2, resulting in apoptosis or NF-κB–dependent activation of inflammatory genes or events leading to lymphoid neogenesis. Many current studies have been confirmed that TNF-β gene polymorphism is associated various malignant diseases. In this study, we investigated the possible association of TNF-β gene polymorphism with colorectal cancer in Taiwan region. Using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), the allele frequency of the TNF-β polymorphism was investigated in 55 patients with colorectal cancer and 134 healthy control ( group IIA, without disease risks, n = 58; group IIB, personnel don’t have any conventional cardiovascular disease risk factors, n = 76). Experimental results show that TNF-β G/G genotype homozygous vs AG + AA genotype in both the experimental group CRC and control group IIA have significant difference (P-value = 0.035). Our study presents preliminary but intriguing data suggesting that TNF-β NcoI may be associated with CRC formation in Taiwan region.

並列關鍵字

tumor necrosis factor beta ； polymorphism ； colorectal cancer

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