中国东部地区人群APE1／Ref-1基因启动子-141T／G遗传变异与脑胶质瘤临床研究

目的研究中国东部地区人群APEl／Ref-1基因启动子-141T／G遗传变异与脑胶质瘤相关性。方法采用MassARRAY SequenomSNP时间飞行质谱生物芯片系统检测中国东部766例胶质瘤患者（241例胶质母细胞瘤，284例星型细胞瘤l～3级，241例其他胶质瘤）和824例非肿瘤对照组的APEl／Ref-1-141T／G多态性。并使用非条件logistic回归分析计算比数比（ORs）和95％可信区间（CIs）。结果APEl／Ref-1基因启动子-141T／G多态性与胶质瘤之间无明显联系。组织学分层分析结果提示等位基因G显著降低胶质瘤风险（OR=0．80，95％CI=0．65～0．98，P=0．032）。与携带TT个体相比，携带-141GG基因型的个体患胶质母细胞瘤的风险低（OR=0．54，95％CI 0．34～0．87，P=0．012）。结论APE1／Ref-1启动子特异遗传变异可能调节个体胶质母细胞瘤而非其他类型胶质瘤的发生风险。

A genetic variant in APE1/Ref-1 gene promoter -141T/G may modulate risk of glioblastoma in population of east of China

Objective To investigate the association of APE1/Ref-1 gene promoter -141T/G polymorphism with individual susceptibility to gliomas in population of east of China. Methods The APE1/Ref-1 -141T/G polymorphism was analyzed in 766 glioma patients （including 241 cases of glioblastoma, 284 astrocytomas and 241 other gliomas ） and 824 non-cancer subjects from eastern China. Genotyping was performed with Sequenom MassARRAY iPLEX platform by use of allele- specific MALDI-TOF mass spectrometry assay. The odds ratios （ORs） and 95% confidence intervals （95% CIs ） were estimated by using unconditional logistic regression. Results The significant association between APE1/Ref-1 promoter -141T/G polymorphism and glioma risk was not observed. However, the stratified analysis by histology revealed the variant allele G significantly decreased glioblastoma risk （OR =0.80, 95% CI =0.65 -0.98, P =0.032）. Individuals with the homozygous141GG genotype exhibited reduced risk of glioblastoma （ adjusted OR = 0.54, 95 % CI = 0.34 - 0.87, P = 0. 012 ） compared with the TT homozygote. Conclusion Our results suggest that a specific genetic variant located in the APE1/Ref-1 promoter may modulate risk of glioblastoma, but not for other histological gliomas. Larger studies with more APE1 polymorphisms are required to validate these preliminary findings.