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目的:胰岛素样生长因子(insulin-like growth factor 1,IGF1)和胰岛素样生长因子结合蛋白-3(IGF binding protein 3,IGFBP3)在肾细胞癌的发生发展中起重要作用。本研究旨在探索位于IGF1和IGFBP3基因功能区具有潜在功能学的基因遗传多态性与中国人群肾癌易感性的关系。方法 :采用病例-对照研究方法,对1 027例肾癌患者和1 094例健康对照,应用Taq Man探针分型法对位于IGF1和IGFBP3基因功能区9个基因遗传多态性位点进行分型。控制混杂因素,应用非条件逻辑回归,评价基因多态性与肾癌易感性之间的关系。结果:在9个基因多态性位点中,通过校正后的多因素分析发现位于IGF1 3′-UTR区域的rs5742714多态性和中国人群肾癌发病风险明显相关。与携带IGF1 rs5742714 GG基因型的个体相比,IGF1 rs5742714 GC/CC基因型携带者的肾癌发病风险明显增高(OR=0.82;95%CI=0.68~0.98,P=0.002)。此外,IGF1 rs5742714 GC/CC基因型癌旁组织中IGF1 m RNA含量明显降低。结论:位于IGF1 3′-UTR区域的rs5742714多态性可能通过调控IGF1基因的表达而影响中国人群肾癌发病易感性。
OBJECTIVE: Insulin-like growth factor 1 (IGF1) and insulin-like growth factor-binding protein-3 (IGFBP3) play an important role in the development of renal cell carcinoma. The purpose of this study was to explore the relationship between potential genetic polymorphisms of IGF1 and IGFBP3 functional regions and susceptibility to renal cell carcinoma in Chinese population. Methods: A case-control study was conducted in 1027 kidney cancer patients and 1 094 healthy controls using TaqMan probe typing to characterize the genetic polymorphisms of nine genes located in the functional regions of IGF1 and IGFBP3 type. Control of confounders, the use of non-conditional logistic regression, evaluation of genetic polymorphisms and renal cell carcinoma of the relationship between susceptibility. Results: In the 9 polymorphic loci, the rs5742714 polymorphism located in the IGF1 3’-UTR region was found to be significantly associated with the risk of kidney cancer in Chinese population by multivariate analysis. Patients with IGF1 rs5742714 GC / CC genotype had a significantly higher risk of developing renal cell carcinoma (OR = 0.82; 95% CI = 0.68-0.98, P = 0.002), compared with individuals carrying the IGF1 rs5742714 GG genotype. In addition, the levels of IGF1 m RNA in the paracancerous tissues of the IGF1 rs5742714 GC / CC genotype were significantly lower. Conclusion: rs5742714 polymorphism located in the 3’-UTR region of IGF1 may affect the susceptibility of Chinese population to renal cell carcinoma by regulating the expression of IGF1 gene.