Xu Qiang, Zhang Zuofu, Sun Weixue, Hu Baiqiang
Department of Joint surgery, Yantai Yuhuangding Hospital, Yu Road, No. 20, Zhifu District, Yantai, 264000, Shandong, China.
Mamm Genome. 2017 Jun;28(5-6):227-233. doi: 10.1007/s00335-017-9693-8. Epub 2017 May 4.
The purpose of the study was to investigate the association of single-nucleotide polymorphisms (SNPs) within excision repair cross-complementation (ERCC) gene polymorphisms, additional gene-gene interaction, and haplotype combination with osteosarcoma risk. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs. Logistic regression was performed to investigate the association between six SNPs within ERCC gene, additional gene-gene interaction on osteosarcoma risk. Haplotype analysis was performed using SNPstats ( http://bioinfo.iconcologia.net/SNPstats ). Osteosarcoma risk was significantly higher in carriers with the T allele of ERCC2-rs1799793 than those with GG genotype (GT+ TT vs. GG), adjusted OR (95% CI) = 1.56 (1.13-2.01), and higher in carriers with the A allele of ERCC3-rs4150441 than those with GG genotype (GA+ AA vs. GG), adjusted OR (95% CI) = 1.63 (1.25-2.09). GMDR model indicated a significant two-locus model (p = 0.0107) involving rs1799793 and rs4150441; cross-validation consistency of the two-locus model was 9/10; and the testing accuracy was 60.11%. Participants rs1799793-GT or -TT and rs4150441-GA or -AA genotype have the highest osteosarcoma risk, compared to subjects with rs1799793-GG and rs4150441-GG genotype, OR (95% CI) = 2.87 (1.21-4.63), after covariates adjustment. Haplotype containing the rs1799793-T and rs11615-T alleles was associated with a statistically increased osteosarcoma risk, OR (95% CI) = 1.47 (1.12-1.92). We found that the T allele of ERCC2-rs1799793 and the A allele of ERCC3-rs4150441, interaction between rs1799793 and rs4150441, and haplotype containing the rs1799793T and rs11615-T alleles were all associated with increased osteosarcoma risk.
本研究的目的是调查切除修复交叉互补（ERCC）基因多态性中的单核苷酸多态性（SNP）、其他基因-基因相互作用以及单倍型组合与骨肉瘤风险之间的关联。使用广义多因素降维法（GMDR）筛选SNP之间的最佳相互作用组合。进行逻辑回归以研究ERCC基因内的6个SNP、其他基因-基因相互作用与骨肉瘤风险之间的关联。使用SNPstats（http://bioinfo.iconcologia.net/SNPstats）进行单倍型分析。与GG基因型携带者相比，携带ERCC2-rs1799793的T等位基因的携带者发生骨肉瘤的风险显著更高（GT + TT vs. GG），校正后的比值比（95%可信区间）= 1.56（1.13 - 2.01），并且携带ERCC3-rs4150441的A等位基因的携带者发生骨肉瘤的风险高于GG基因型携带者（GA + AA vs. GG），校正后的比值比（95%可信区间）= 1.63（1.25 - 2.09）。GMDR模型显示涉及rs1799793和rs4150441的显著两位点模型（p = 0.0107）；两位点模型的交叉验证一致性为9/10；检验准确性为60.11%。与rs1799793-GG和rs4150441-GG基因型的受试者相比，rs1799793为GT或TT且rs4150441为GA或AA基因型的参与者患骨肉瘤的风险最高，校正协变量后，比值比（95%可信区间）= 2.87（1.21 - 4.63）。包含rs1799793-T和rs11615-T等位基因的单倍型与骨肉瘤风险的统计学显著增加相关，比值比（95%可信区间）= 1.47（1.12 - 1.92）。我们发现ERCC2-rs1799793的T等位基因、ERCC3-rs4150441的A等位基因、rs1799793和rs4150441之间的相互作用以及包含rs1799793T和rs11615-T等位基因的单倍型均与骨肉瘤风险增加相关。
