Cancer Genetics and Epigenetics Lab, Department of Biosciences, COMSATS Institute of Information Technology (CIIT), Park Road, Chak shazad Islamabad, Pakistan.
Sci Rep. 2017 Oct 16;7(1):13210. doi: 10.1038/s41598-017-13461-6.
We aimed to investigate the effect of hotspot variations of XRCC2 gene on the risk of head and neck cancer (HNC) in 400 patients and 400 controls. Five polymorphisms of XRCC2 gene G4234C (rs3218384), G4088T (rs3218373), G3063A (rs2040639), R188H (rs3218536) and rs7802034 were analyzed using Allele- specific polymerase chain reaction (ARMS-PCR) followed by sequence analysis. For rs3218373, the GG genotype indicated a statistically significant 3-fold increased risk of HNC (P < 0.001) after multivariate adjustment. For rs7802034, the GG genotype suggested statistically significant 2-fold increased risk of HNC (P < 0.001). For SNP of rs3218536, the AA genotype indicated a significant 3-fold increased risk of HNC (P < 0.001). Additionally, haplotype analysis revealed that TACAG, TGGAG, TACGG and TAGGA haplotypes of XRCC2 polymorphisms are associated with HNC risk. Two SNPs in XRCC2 (rs2040639 and rs3218384) were found increased in strong linkage disequilibrium. Furthermore, joint effect model showed 20 fold (OR = 19.89; 95% CI = 2.65-149.36, P = 0.003) increased HNC risk in patients carrying four homozygous risk alleles of selected polymorphisms. These results show that allele distributions and genotypes of XRCC2 SNPs are significantly associated with increased HNC risk and could be a genetic adjuster for the said disease.
我们旨在研究 XRCC2 基因热点变异对 400 例患者和 400 例对照者头颈部癌症（HNC）风险的影响。采用等位基因特异性聚合酶链反应（ARMS-PCR）结合序列分析方法，对 XRCC2 基因 G4234C（rs3218384）、G4088T（rs3218373）、G3063A（rs2040639）、R188H（rs3218536）和 rs7802034 共 5 个多态性进行分析。rs3218373 多态性经多因素校正后，GG 基因型提示 HNC 发生风险增加 3 倍（P<0.001）。rs7802034 多态性 GG 基因型提示 HNC 发生风险增加 2 倍（P<0.001）。rs3218536 多态性 AA 基因型提示 HNC 发生风险增加 3 倍（P<0.001）。此外，单体型分析显示 XRCC2 多态性的 TACAG、TGGAG、TACGG 和 TAGGA 单体型与 HNC 风险相关。在 XRCC2 中发现 2 个 SNP（rs2040639 和 rs3218384）存在强连锁不平衡。此外，联合效应模型显示，携带所选多态性 4 个纯合风险等位基因的患者 HNC 发病风险增加 20 倍（OR=19.89；95%CI=2.65-149.36，P=0.003）。这些结果表明，XRCC2 SNP 的等位基因分布和基因型与 HNC 风险增加显著相关，可能是该疾病的遗传调节剂。
