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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 33-39 |
| Number of pages | 7 |
| Journal | Journal of Neuro-Oncology |
| Volume | 136 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2018 |
Funding
Funding D.I.J. is supported by the CPRIT Post-Graduate Training Program in Integrative Cancer Epidemiology (Award ID RP160097). Work at MD Anderson Cancer Center and Baylor College of Medicine was supported by National Institutes of Health Grants R01 CA120813 to A.B.H, P50 CA127001 to A.B.H, R01 CA119215 to M.L.B, R01 CA070917 to M.L.B, R01 CA139020 to M.L.B, and K07 CA181480 to Y.L; American Brain Tumor Association to M.L.B, The National Brain Tumor Society to M.L.B, and The Dr. Marnie Rose Foundation to A.B.H. Work at University of California, San Francisco was supported by the National Institutes of Health (Grant Numbers R01CA52689, P50CA097257, and R01CA139020), as well as the loglio Collective, the National Brain Tumor Foundation, the Stanley D. Lewis and Virginia S. Lewis Endowed Chair in Brain Tumor Research, the Robert Magnin Newman Endowed Chair in Neuro-oncology, and by donations from families and friends of John Berardi, Helen Glaser, Elvera Olsen, Raymond E. Cooper, and William Martinusen. We are grateful to all of the patients and individuals for their participation, and we would also like to thank the clinicians and other hospital staff members, cancer registries and the study staff members in the respective centers who contributed to the data collection. This publication was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 RR024131. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute?s Surveillance, Epidemiology and End Results Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute; and the Centers for Disease Control and Prevention?s National Program of Cancer Registries, under agreement # U58DP003862-01 awarded to the California Department of Public Health. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California Department of Public Health, the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors is not intended nor should be inferred. We thank David M. Wildrick, Ph.D., for editorial assistance with the manuscript. D.I.J. is supported by the CPRIT Post-Graduate Training Program in Integrative Cancer Epidemiology (Award ID RP160097). Work at MD Anderson Cancer Center and Baylor College of Medicine was supported by National Institutes of Health Grants R01 CA120813 to A.B.H, P50 CA127001 to A.B.H, R01 CA119215 to M.L.B, R01 CA070917 to M.L.B, R01 CA139020 to M.L.B, and K07 CA181480 to Y.L; American Brain Tumor Association to M.L.B, The National Brain Tumor Society to M.L.B, and The Dr. Marnie Rose Foundation to A.B.H. Work at University of California, San Francisco was supported by the National Institutes of Health (Grant Numbers R01CA52689, P50CA097257, and R01CA139020), as well as the loglio Collective, the National Brain Tumor Foundation, the Stanley D. Lewis and Virginia S. Lewis Endowed Chair in Brain Tumor Research, the Robert Magnin Newman Endowed Chair in Neuro-oncology, and by donations from families and friends of John Berardi, Helen Glaser, Elvera Olsen, Raymond E. Cooper, and William Martinusen. All of the authors have declared no conflict of interest. Acknowledgements We are grateful to all of the patients and individuals for their participation, and we would also like to thank the clinicians and other hospital staff members, cancer registries and the study staff members in the respective centers who contributed to the data collection. This publication was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 RR024131. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute’s Surveillance, Epidemiology and End Results Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute; and the Centers for Disease Control and Prevention’s National Program of Cancer Registries, under agreement # U58DP003862-01 awarded to the California Department of Public Health. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California Department of Public Health, the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors is not intended nor should be inferred. We thank David M. Wildrick, Ph.D., for editorial assistance with the manuscript.
Keywords
- Genetic polymorphism
- Glioblastoma
- Glioma
- Glioma-associated myeloid cells
- Immune suppression
- Survival
ASJC Scopus subject areas
- Clinical Neurology
- Neurology
- Oncology
- Cancer Research
