Germline polymorphisms in myeloid-associated genes are not associated with survival in glioma patients

Abstract

Immune cells of myeloid origin, including microglia, macrophages, and myeloid-derived suppressor cells adopt immunosuppressive phenotypes that support gliomagenesis. Here, we tested an a priori hypothesis that single nucleotide polymorphisms (SNPs) in genes related to glioma-associated myeloid cell regulation and function are also associated with patient survival after glioma diagnosis. Subjects for this study were 992 glioma patients treated at The University of Texas MD Anderson Cancer Center in Houston, Texas between 1992 and 2008. Haplotype-tagging SNPs in 91 myeloid-associated genes were analyzed for association with survival by Cox regression. Individual SNP- and gene-based tests were performed separately in glioblastoma (WHO grade IV, n = 511) and lower-grade glioma (WHO grade II-III, n = 481) groups. After adjustment for multiple testing, no myeloid-associated gene variants were significantly associated with survival in glioblastoma. Two SNPs, rs147960238 in CD163 (p = 2.2 × 10^-5) and rs17138945 in MET (p = 5.6 × 10^-5) were significantly associated with survival of patients with lower-grade glioma. However, these associations were not confirmed in an independent analysis of 563 lower-grade glioma cases from the University of California at San Francisco Adult Glioma Study (p = 0.65 and p = 0.41, respectively). The results of this study do not support a role for inherited polymorphisms in myeloid-associated genes in affecting survival of patients diagnosed with glioblastoma or lower-grade glioma.

Keywords: Genetic polymorphism; Glioblastoma; Glioma; Glioma-associated myeloid cells; Immune suppression; Survival.

Figure 1

Association of variants in myeloid-associated genes with survival in glioma patients. Dots represent SNPs tested for association in the corresponding myeloid-associated gene with survival of glioblastoma patients or lower-grade glioma patients, and they are plotted according to the −log₁₀(p value) from single-SNP tests. A significance level of p = 0.001 is denoted by the dotted line, and SNPs with False Discovery Rate-adjusted p values < 0.10 are colored in red.