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RAD51基因135位G/C、172位G/T多态性及XRCC3基因Thr241Met多态性与头颈癌风险增加的相关性

Association of RAD 51 135 G/C, 172 G/T and XRCC3 Thr241Met gene polymorphisms with increased risk of head and neck cancer.

作者信息

Kayani Mahmood Akhtar, Khan Sumeera, Baig Ruqia Mehmood, Mahjabeen Ishrat

机构信息

Department of Biosciences, COMSATS Institute of Information and Technology, Islamabad, Pakistan E-mail :

出版信息

Asian Pac J Cancer Prev. 2014;15(23):10457-62. doi: 10.7314/apjcp.2014.15.23.10457.

Abstract

Homologous recombination repair (HRR) plays an important role in protection against carcinogenic factors. Genes regulating the HRR mechanisms may impair their functions and consequently result in increased cancer susceptibility. RAD 51 and XRCC3 are key regulators of the HRR pathway and genetic variability in these may contribute to the appearance and progression of various cancers including head and neck cancer (HNC). The aim of the present study was to compare the distribution of genotypes of RAD51 (135G/C, 172 G/T) and XRCC3 (Thr241Met) polymorphisms between HNC patients and controls. Each polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymerase (PCR-RFLP) technique in 200 pathologically confirmed HNC patients along with 150 blood samples from normal, disease free healthy individuals. We observed that homozygous variant CC genotype of RAD51 135G/C was associated with a 2.5 fold increased HNC risk (OR=2.5; 95%CI=0.69-9.53; p<0.02), while second polymorphism of RAD 51 172 G/T, heterozygous variant GT genotype was associated with a 1.68 fold (OR=1.68; 95%CI=1.08-2.61; p<0.02) elevation when compared with controls. In the case of the Thr241Met polymorphism of XRCC3, we observed a 16 fold (OR=16; 95% CI= 3.78-69.67; p<0.0002) increased HNC risk in patients compared to controls. These results further suggested that RAD51 (135G/C, 172 G/T) and XRCC3 (Thr241Met) polymorphisms may be effective biomarkers for genetic susceptibility to HNC. Larger studies are needed to confirm our findings and identify the underlying mechanisms.

摘要

同源重组修复(HRR)在抵御致癌因素方面发挥着重要作用。调节HRR机制的基因可能会损害其功能,从而导致癌症易感性增加。RAD 51和XRCC3是HRR途径的关键调节因子,它们的基因变异性可能促成包括头颈癌(HNC)在内的各种癌症的发生和发展。本研究的目的是比较HNC患者与对照组之间RAD51(135G/C、172 G/T)和XRCC3(Thr241Met)多态性的基因型分布。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对200例经病理确诊的HNC患者以及150例来自正常、无病健康个体的血样进行各多态性的基因分型。我们观察到,RAD51 135G/C的纯合变异CC基因型与HNC风险增加2.5倍相关(OR=2.5;95%CI=0.69-9.53;p<0.02),而RAD 51 172 G/T的第二个多态性,杂合变异GT基因型与对照组相比风险升高1.68倍(OR=1.68;95%CI=1.08-2.61;p<0.02)。对于XRCC3的Thr241Met多态性,我们观察到与对照组相比,患者的HNC风险增加了16倍(OR=16;95% CI= 3.78-69.67;p<0.0002)。这些结果进一步表明,RAD51(135G/C、172 G/T)和XRCC3(Thr241Met)多态性可能是HNC遗传易感性的有效生物标志物。需要更大规模的研究来证实我们的发现并确定潜在机制。

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