介白素-1 beta 的基因多型性與大腸直腸癌發生率的關聯性

The association of interleukin-1 beta polymorphism with colorectal cancer

蕭珮君(Pei-Chun, Hsiao)

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(2014年)

https://doi.org/10.6834/CSMU.2014.00140

摘要

大腸直腸癌是全世界女性排名第二位，男性排名為第三位常見的癌症。而危險因子包括了：高比例紅肉攝取、高脂低纖維飲食、飲酒、抽菸、肥胖、年齡、性別、潰瘍性腸炎以及有大腸直腸癌家族史者。IL-1 beta蛋白有多效性的生物功能，包括增強發炎細胞從血液移動到發炎組織以及調控細胞外基質降解來調節發炎反應。之前有許多研究指出單核酸多型性與多種疾病與癌症有關聯性。亦有許多研究報導發炎反應與癌症有密切的關聯，因此本次實驗目的要研究貝他型介白素 IL-1 beta -511 單核酸多型性與台灣人口大腸直腸癌的相關性。利用聚合酶連鎖反應-限制酶切割片段長度多型性的方法，來分析62位大腸直腸癌患者及134位年齡相仿的對照組（IIA，58位，有疾病風險；IIB，76位，無疾病風險），其IL-1 beta基因多型性等位基因頻率的關聯性。結果顯示IL-1 beta- 511 基因多型性在大腸直腸癌患者與對照組間並無顯著性差異(21.0％ vs. 25.4％，p＝0.501）。此外，大腸直腸癌實驗組中，IL-1 beta -511同型合子C/C等位基因與T/T+T/C基因型頻率與腫瘤分期 （p = 0.764）、腫瘤大小 ( p = 0.241)、近端淋巴轉移( p = 0.499)、患者的復發率（p = 0.689）以及存活率( p = 0.329) 均無顯著性的差異。然而，在大腸直腸癌實驗組中C/C同型合子及T/T+T/C基因型的頻率與腫瘤遠端轉移間有顯著性差異( p = 0.050)。本次的研究首次提出在台灣人口中，大腸直腸癌的遠端轉移與IL-1 beta -511基因多型性是具有相關性的。

關鍵字

介白素-1 貝他型基因多型性 ； 大腸直腸癌

並列摘要

Globally colorectal cancer (CRC) is the second most common cancer in women and the third most common in men. The risk factors for CRC including：high red meat consumption、high fat low fiber diet、alcohol、tobacco consumption、obesity、age、gender、ulcerative colitis (UC) and family history of CRC . The IL-1 beta protein has many pleiotropic biological functions, including the mediation of inflammation by enhancing the movement of inflammatory cells from the blood to inflamed tissues and the regulation of extracellular matrix degradation . There are many reports indicated that single nucleotide polymorphism （SNP）are associated with cancers and diseases . Given the previous reports concerning the possible association with inflammation and cancer，we studied the association of the IL-1 beta -511 C/T polymorphism and CRC in Taiwan population . Using polymerase chain reaction and restriction fragment length polymorphism（PCR–RFLP），the allele frequency of the IL-1 beta polymorphism was investigated in 62 patients with colorectal cancer and 134 age matched control ( group IIA，with disease risks，n = 58； group IIB，without disease risks，n = 76) . It shows that polymorphism of IL-1 beta -511 in between CRC patients and controls are not significant difference (21.0％ vs. 25.4％，p＝0.501) . In addition，the frequencies of IL-1 beta -511 homozygous C/C allele and T-carrier (T/T+T/C) genotype in CRC group was not associated with stage ( p = 0.764)、tumor size ( p = 0.241) 、lymph node metastasis ( p = 0.499) 、recurrence（ p = 0.689）and survival ( p = 0.329) . However，in CRC group there is a significantly difference between the frequency of C/C homozygous allele compared to T-carrier (T/T+T/C) genotype (p = 0.050) in distant metastasis. Our study presents preliminary but intriguing data suggesting that polymorphism in IL-1 beta -511 might be associated with the metastasis of CRC in Taiwan population.

並列關鍵字

interleukin-1 beta polymorphism ； colorectal cancer

參考文獻

1. Ozdemir Y, Akin ML, Sucullu I, Balta AZ, Yucel E: Pretreatment neutrophil/lymphocyte ratio as a prognostic aid in colorectal cancer. Asian Pacific journal of cancer prevention : APJCP 2014, 15(6):2647-2650.

2. Courtney RJ, Paul CL, Sanson-Fisher RW, Macrae FA, Carey ML, Attia J, McEvoy M: Colorectal cancer risk assessment and screening recommendation: a community survey of healthcare providers' practice from a patient perspective. BMC family practice 2012, 13:17.

3. Bardhan K, Liu K: Epigenetics and colorectal cancer pathogenesis. Cancers 2013, 5(2):676-713.

4. Ingram N, Northwood EL, Perry SL, Marston G, Snowden H, Taylor JC, Scott N, Bishop DT, Coletta PL, Hull MA: Reduced type II interleukin-4 receptor signalling drives initiation, but not progression, of colorectal carcinogenesis: evidence from transgenic mouse models and human case-control epidemiological observations. Carcinogenesis 2013, 34(10):2341-2349.

5. Terzic J, Grivennikov S, Karin E, Karin M: Inflammation and colon cancer. Gastroenterology 2010, 138(6):2101-2114 e2105.