SET8基因3’非翻译区miR-502结合位点单核苷酸多态性与肾透明细胞癌发病风险的关系

Polymorphism at the miR-502 binding site in the 3＇ untranslated region of SET8 gene is associated with the risk of clear cell renal cell carcinoma

目的探讨SET8基因3‘非翻译区miR．502结合位点单核苷酸多态性与肾透明细胞癌发病风险的关系。方法采用病例对照研究的方法．对140例肾透明细胞癌患者和130例健康对照者的SET8基因3’非翻译区miR一502结合区域的rsl6917496位点进行测序，分析rs16917496位点的基因型与肾透明细胞癌患病风险的关系。采用免疫组织化学法检测不同基因型肾透明细胞癌患者肿瘤组织中SET8蛋白的表达情况，分析SET8蛋白的表达与rsl6917496位点基因型的关系。结果140例肾透明细胞癌患者中，SET8基因3’非翻译区miR．502结合位点rsl6917496CC、CT和1Tr基因型分别为14、47和79例；130例健康体检者中，SET8基因3’非翻译区miR．502结合位点rsl6917496CC、CT和TT基因型分别为30、32和68例。与健康体检者比较，肾透明细胞癌患者CT、TF基因型出现的频率明显增高（均P〈0．05）。携带cT、TT基因型者患肾透明细胞癌的风险明显增高（均P〈O．05）。SET8基因3’非翻译区miR．502结合位点rsl6917496位点的CT和TT基因型与SET8蛋白的高表达有关（P〈0．05）。结论SET8基因3’非翻译区miR一502结合区域rsl6917496位点的基因型与SET8蛋白的表达有关，该位点的单核苷酸多态性有利于确定肾透明细胞癌的易感性。

Objective To investigate the relationship between single nucleotide polymorphism of SET8 gene and the risk of clear cell renal cell carcinoma （CCRCC）. Methods We selected 140 CCRCC patients and 130 healthy controls in this case-control study. Genotype of single nucleotide polymorphism （rs16917496） at the miR-502 binding site in the 3＇UTR of SET8 mRNA in the CCRCC patients and healthy controls was tested and the association between genotype and risk of cancer was assessed. The expression of SET8 was determined by immunohistochemistry and the relationship between expression of SET8 and genotype of rs16917496 was analyzed. Results In the control group, CC, CT and TT genotypes were found in 30, 32 and 68 persons, respectively, while in the CCRCC patients, CC, CT and TT genotypes were found in 14 , 47 and 79 cases, respectively.The frequencies of rs16917496 CT and TF genotypes in the CCRCC group were significantly higher than those in the control group （P〈0.05）. Compared with the CC genotype, patients with CT and TF genotypes were more susceptible to develop CCRCC （P 〈 0.05 ）. CT and TT genotypes of rs16917496 at the miR-502 binding site of the SET8 gene were associated with expression of SET8. Conclusions Genotype of the SNP rs16917496 at the miR-502 binding site in the 3＇ untranslated region of the SET8 gene is associated with the expression of SET8 protein. Analysis of genetic polymorphisms in miRNA binding sites may help to identify the subgroups of population susceptible to CCRCC.