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XRCC3单倍型与中国人群胶质瘤风险:一项基于医院的病例对照研究。

XRCC3 haplotypes and risk of gliomas in a Chinese population: a hospital-based case-control study.

作者信息

Zhou Keke, Liu Yanhong, Zhang Haishi, Liu Hongliang, Fan Weiwei, Zhong Yu, Xu Zhonghui, Jin Li, Wei Qingyi, Huang Fengping, Lu Daru, Zhou Liangfu

机构信息

Neurosurgery Department of Huashan Hospital, Fudan University, Shanghai, China.

出版信息

Int J Cancer. 2009 Jun 15;124(12):2948-53. doi: 10.1002/ijc.24307.

Abstract

In mammalian cells, X-ray repair cross-complementing group3 (XRCC3) plays an important role in the DNA double-strand breaks (DSBs) repair by homologous recombination. Genetic polymorphisms in the XRCC3 gene may potentially affect the repair of DSBs and thus confer susceptibility to gliomas. In this study, we used a haplotype-based approach to investigate whether 4 tagging single nucleotide polymorphisms of the XRCC3 gene are associated with risk of gliomas in 771 glioma patients and 752 cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the unconditional logistic regression, and haplotype associations were estimated using Haplo.Stat. After adjustment for age and sex, the variant G allele of rs861530 and T allele of rs3212092 were significantly associated with an increased risk of gliomas (AG/GG versus AA: adjusted OR = 1.44, 95% CI = 1.15-1.80, p = 0.001 and CT/TT versus CC: adjusted OR = 1.66, 95% CI = 1.12-2.46, p = 0.013, respectively). Consistent with these results, XRCC3 haplotype "GGCC" containing rs861530 G allele and haplotype "AGTC" containing rs3212092 T allele were also significantly associated with an elevated risk of gliomas compared with the common haplotype "AGCC" (adjusted OR = 1.35, 95% CI = 1.14-1.58, p = 0.000 and adjusted OR = 1.67, 95% CI = 1.11-2.52, p = 0.015, respectively). Our results suggest that common genetic variants in the XRCC3 gene may modulate glioma risk.

摘要

在哺乳动物细胞中,X射线修复交叉互补基因3(XRCC3)在通过同源重组修复DNA双链断裂(DSB)过程中发挥重要作用。XRCC3基因的遗传多态性可能会影响DSB的修复,从而使人易患胶质瘤。在本研究中,我们采用基于单倍型的方法,调查XRCC3基因的4个标签单核苷酸多态性是否与771例胶质瘤患者和752例无癌对照者患胶质瘤的风险相关。通过无条件逻辑回归计算比值比(OR)和95%置信区间(CI),并使用Haplo.Stat估计单倍型关联。在对年龄和性别进行校正后,rs861530的变异G等位基因和rs3212092的T等位基因与患胶质瘤风险增加显著相关(AG/GG与AA相比:校正OR = 1.44,95% CI = 1.15 - 1.80,p = 0.001;CT/TT与CC相比:校正OR = 1.66,95% CI = 1.12 - 2.46,p = 0.013)。与这些结果一致,与常见单倍型“AGCC”相比,包含rs861530 G等位基因的XRCC3单倍型“GGCC”和包含rs3212092 T等位基因的单倍型“AGTC”也与患胶质瘤风险升高显著相关(校正OR分别为1.35,95% CI = 1.14 - 1.58,p = 0.000;校正OR = 1.67,95% CI = 1.11 - 2.52,p = 0.015)。我们的结果表明,XRCC3基因的常见遗传变异可能会调节胶质瘤风险。

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