Association of polymorphisms in FLT3, EGFR, ALOX5, and NEIL3 with glioblastoma in the Han Chinese population

Abstract

Glioblastoma (GBM) is the highest-grade glioma in astrocytoma. Patients often have poor prognosis due to therapeutic resistance and tumor recurrence. Identification of the genetic factors of GBM could be important contribution to early prevention of this disease. We genotyped 17 tag single-nucleotide polymorphisms (tSNPs) from nine genes in this study, including 72 cases and 302 controls. SNP genotyping was conducted using Sequenom MassARRAY RS1000. Statistical analysis of the association between tSNPs and GBM was performed using the χ (2) test and SNPStats software. The rs3829382 in FLT3 was associated with increased odds of developing GBM using the χ (2) test. When we analyzed tSNPs under different inheritance models, we found rs9642393 in EGFR increased odds of developing GBM in the dominant model. After stratification by gender, we found that rs12645561 in NEIL3 and rs2291427 in ALOX5 were associated with developing GBM. Polymorphisms within FLT3, EGFR, NEIL3, and ALOX5 may contribute to the occurrence of GBM in the Han Chinese population. However, the functional significance of these polymorphisms needs further investigation.

Genetic variants in the DNA repair gene NEIL3 and the risk of myocardial infarction in a nested case–control study. The HUNT Study

“…Also, a genome-wide linkage study demonstrated an association between several NEIL3 SNPs and type 2 diabetes [35]. Interestingly, the NEIL3 SNP found to be associated with MI in our study, rs12645561, has previously been shown to be associated with the risk of developing glioma [36] and glioblastoma [37]. The molecular interpretation of this SNP is at present not clear, given its genomic location in the splice site between exons 4 and 5.…”

Genetic variants and risk of prostate cancer using pathway analysis of a genome-wide association study

“…It has been proposed that NEIL3 may be a potential tumor suppressor gene of hepatocellular carcinoma [15]. In addition, previous studies reported that NEIL3 SNP rs12645561 was associated with the risk of developing glioma and glioblastoma [16,17]. These observations may suggest that NEIL3 is required for the maintenance of cancer cell growth or the progression of malignancy, and that it may play a role in DNA repair as a tumor suppressor gene.…”

FEN1gene variants confer reduced risk of breast cancer in chinese women: A case-control study

“…Two tag SNPs (rs4246215 and rs174538), which captured the majority of the known common variation in FEN1 according to the data on the Chinese population from HapMap (http://www.hapmap.org), were selected in our study. Sequenom MassARRAY Assay Design 3.0 Software (Agena Bioscience, San Diego, CA, USA) was used to design a multiplexed SNP MassEXTEND assay [25]. SNP genotyping was performed using the Sequenom MassARRAY RS1000 according to the standard protocol recommended by the manufacturer.…”

“…The corresponding primers used for each SNP in our study are listed in Table 8. Sequenom Typer 3.0 Software was used for data analyses [25, 26]. …”