Haplotype analysis on relationship of ERCC2 and ERCC3 gene polymorphisms with osteosarcoma risk in Chinese young population

Abstract

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.

Epidemiological Evidence for Associations Between Genetic Variants and Osteosarcoma Susceptibility: A Meta-Analysis

“…Single nucleotide polymorphisms (SNPs) have been reported to be involved in DNA repair, growth regulation, antigen processing and presentation, which may be implicated in the pathogenesis of OS (6)(7)(8). Genetic variants, such as VEGF rs2010963, ERCC rs1800795, and IL6 rs1800795, have been found to be related to the susceptibility of lung cancer, gastric cancer, and OS (9)(10)(11). Genetic variation plays crucial roles in the pathogenesis of OS and elucidating relationships between genetic variation and OS susceptibility is critical to improve the therapeutic strategies (6,7).…”

Overexpression of ERCC3 is associated with poor prognosis in patients with pancreatic cancer

“…Recent evidence revealed elevated ERCC3 expression in epithelial ovarian cancer and hepatocellular carcinoma [10,11]. Moreover, the genetic variants in ERCC3 may contribute to the development of breast cancer [12], lung cancer [13], osteosarcoma [14], and bladder cancer [15]. In addition, testing of triptolide in conditionally reprogrammed patient-derived carcinoma revealed ERCC3-MYC interactions and variable sensitivity between lines [16].…”