However, Bonferroni corrections are considered acceptable when performing associations without pre-established hypotheses. Another potential concern was population admixture, which is a known confounding factor for association analysis and can caused inflated type-I errors. In this study, glioma patients and controls were used in the same hospital to avoid selection bias. However, this bias was unlikely to be of significance because the patient groups did not differ in the distributions of demographic variables and genotype frequencies. We limited all subjects’ ethnicity to Han Chinese, and a living area to Xi’an City and its surrounding area, thus there was no substantial population admixture in our study populations. Our findings in this study provided new evidence for the association between SNPs and haplotypes of the EGFR gene and the risk of glioma. The EGFR gene is highly variable, and both EGFR gene amplification and mutation have been frequently observed in glioblastoma tumors. EGFR signaling is initiated by ligand binding to the extracellular ligand-binding domain, which initiates receptor homo-/hetero-dimerization and auto- The EGFR gene has been reported as one of the major genes responsible for malignant progression and phenotype. However, the mechanism how germline EGFR variants contribute to gliomagenesis remains unclear. Since EGFR gene amplifications were observed commonly in glioblastoma multiform, we hypothesized that certain mutations or haplotypes rendered the receptor susceptible to EGFR amplification. In future studies, to uncover the role of the EGFR gene in gliomagenesis, serum EGFR expression levels between different mutations or haplotype groups will be compared. We will also investigate the association between germline EGFR variants and somatic EGFR mutations, and the relationship between serum EGFR expression and somatic EGFR expression in the same glioma subjects. In conclusion, our comprehensive analysis of SNPs in the EGFR gene suggests that EGFR genotypes and haplotypes are associated with glioma risk. These findings indicate that germ-line genetic variants of the EGFR gene play a complex role in the development of glioma, and that interactions of loci in the EGFR gene may be more important than a single locus. Our study offers important insights into the etiology of glioma.phosphorylation by the intracellular kinase domain, resulting in receptor activation. The EGFR gene was identified to be MK-2206 instrumental in glioma formation by EGFR transgenic rats that developed cerebellar glioma. In a previous study, a polymorphism in the 59-untranslated region of the epidermal growth factor gene, a natural ligand of the EGFR, was identified to play an important role in the pathogenesis of malignant gliomas. They found that patients with the “GA” or “GG” genotype had higher EGF levels, irrespective of the EGFR status, were more likely to recur after surgery, and had a statistically significant shorter overall progression-free survival than patients with the “AA” genotype.