Detection Of Nasopharyngeal Carcinoma Susceptive Single Nucleotide Polymorphisms By The Next-generation Sequencing Technology

Objective: Tumor is a polygenic hereditary disease. Nasopharyngeal carcinoma(NPC) is a kind of head and neck neoplasms, with high incidence in South China and East Asia. Host genetics factors play important roles in NPC pathogenesis. Single nucleotide polymorphism(SNP) is the third generation genetic marker after restrictionfragment length polymorphism and microsatellite polymorphism. The study of SNP is benefical to the understanding of disease pathogenesis, diagnosis, individual treatment and disease susceptibility. Next-generation sequencing technology(NGS) is a new high-throughput sequencing technology, which can detect hundreds of thousands to millions genetic molecules at a time. NGS is much more convenient than the traditional genetic testing technologies such as polymerase chain reaction(PCR) and probe hybridization technology. Therefore, to get NPC susceptive SNP and provide theoretical basis for early prevention and screening of NPC, we designed to detect NPC susceptive SNP by NGS. Methods: A comprehensive search of Pub Med, Web of Science, and SD database for the period up to April 2014 was conducted to identify relevant articles. The articles talking about the same SNP were put together and made meta-analysis to find out statistically significant SNPs. Peripheral venous blood of NPC patients and healthy people in the period of June to July 2014 in the First Affiliated Hospital of Guangdong Pharmaceutical University was collected to do a case-control study to detect the significant SNPs by NGS. Results: 15 significant SNPs were collected after meta-analysis. They were TP53(rs1042522, C>G), GSTM1(+/DEL), IL-10(rs1800896, A>G), GABBR1(rs2076483, T>C), MDM2(rs2279744, T>G), mi R-146a(rs2910164, C>G), MDS1-EVI1(rs6774494, G>A), XPC(rs2228000, C>T), GABBR1(rs29232, G>A), HCG9(rs3869062, A>G), HLA-F(rs3129055, T>C), HCG9(rs16896923, T>C), MMP2(rs243865, C>T), SPLUNC1(rs2752903, T>C), SPLUNC1(rs750064, A>G). The variation of mi R-146a(rs2910164, C>G), HCG9(rs3869062, A>G), HCG9(rs16896923, T>C), MMP2(rs243865, C>T), GABBR1(rs2076483, T>C), TP53(rs1042522, C>G) could contribute to decreased susceptibility to NPC, and the others could contribute to increased susceptibility to NPC. Through the case-control study, the increased risk was found in the AG gene model compared with AA gene model of HCG9(rs3869062, A>G). The variation of GABBR1(rs29232, G>A) might be the protection role in the carcinogenesis of NPC. Genetic deletion of GSTM1 might contribute to increased susceptibility to NPC. No associations were found between the other SNPs and NPC risk. Conclusions: Considering the whole results of the topic, we conclude that the genetic deletion of GSTM1 may contribute to increased susceptibility to NPC, while the variation of HCG9(rs3869062, A>G) and GABBR1(rs29232, G>A) may have some association with NPC risk. Further large and well-designed studies are needed to confirm the association.