Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 May 9;8(1):7352.
doi: 10.1038/s41598-018-24580-z.

Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21

Quinn T Ostrom  1   2   3 , Ben Kinnersley  4 , Margaret R Wrensch  5 , Jeanette E Eckel-Passow  6 , Georgina Armstrong  1 , Terri Rice  5 , Yanwen Chen  2 , John K Wiencke  5 , Lucie S McCoy  5 , Helen M Hansen  5 , Christopher I Amos  7 , Jonine L Bernstein  8 , Elizabeth B Claus  9   10 , Dora Il'yasova  11   12   13 , Christoffer Johansen  14   15 , Daniel H Lachance  16 , Rose K Lai  17   18 , Ryan T Merrell  19 , Sara H Olson  8 , Siegal Sadetzki  20   21 , Joellen M Schildkraut  22 , Sanjay Shete  23 , Joshua B Rubin  24   25 , Justin D Lathia  26 , Michael E Berens  27 , Ulrika Andersson  28 , Preetha Rajaraman  29 , Stephen J Chanock  29   30 , Martha S Linet  29 , Zhaoming Wang  29   30 , Meredith Yeager  29   30 ; GliomaScan consortium; Richard S Houlston  4 , Robert B Jenkins  31 , Beatrice Melin  28 , Melissa L Bondy  1 , Jill S Barnholtz-Sloan  32
Collaborators, Affiliations

Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21

Quinn T Ostrom et al. Sci Rep. .

Abstract

Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.

PubMed Disclaimer

Conflict of interest statement

This study was approved locally by the institutional review board (IRB) at University Hospitals Cleveland Medical Center and by each participating study site’s IRB. Written informed consent was obtained from all participants. There are no conflicts of interest to report. The GliomaScan (phs000652.v1.p1), CGEMS (phs000812.v1.p1), San Francisco Adult Glioma Study (phs001497.v1.p1), and GICC (phs001319.v1.p1) data used for these analyses are available through dbGap. Individual genotypes and phenotypes from the MD Anderson Glioma GWAS are being submitted to dbGAP, and final identifiers to these data will be provided in the final manuscript. The results here are in part based upon data generated by the TCGA Research Network: (http://cancergenome.nih.gov/).

Figures

Figure 1
Figure 1
Average Annual Incidence of all glioma, glioblastoma and lower grade glioma by sex and age at diagnosis (CBTRUS 2010–2014).
Figure 2
Figure 2
Study Schematic for analyses of (A) autosomal SNPs and (B) SNPs on sex chromosomes.
Figure 3
Figure 3
Sex-specific odds ratios overall and by histology grouping, 95% CI and p values for selected previous GWAS hits and 3p21.31 (rs9841110) for all glioma, GBM, and non-GBM.
Figure 4
Figure 4
Manhattan plot of -log(p) values for all glioma in (A) males and (B) females, for GBM in (C) males and (D) females, and for non-GBM in (E) males and (F) females.
Figure 5
Figure 5
Plot of region on chromosome 3 identified as having a sex-specific association with GBM for (A) males and (B) females.
Figure 6
Figure 6
Odds ratios and 95% confidence intervals for unweighted risk (URS) score in (A) all glioma, (B) GBM-specific URS (URS-G) in GBM, and (C) and non-GBM-specific URS (URS-NGBM) for in non-GBM.
See this image and copyright information in PMC

Similar articles

  • The association of 6 variants of 8q24 and the risk of glioma: A meta-analysis.
    Tong Y, Ye L, Li S, Zhao F, Ying J, Qu Y, Li J, Mu D. Tong Y, et al. Medicine (Baltimore). 2019 Jul;98(27):e16205. doi: 10.1097/MD.0000000000016205. Medicine (Baltimore). 2019. PMID: 31277128 Free PMC article. Review.
  • Age-specific genome-wide association study in glioblastoma identifies increased proportion of 'lower grade glioma'-like features associated with younger age.
    Ostrom QT, Kinnersley B, Armstrong G, Rice T, Chen Y, Wiencke JK, McCoy LS, Hansen HM, Amos CI, Bernstein JL, Claus EB, Eckel-Passow JE, Il'yasova D, Johansen C, Lachance DH, Lai RK, Merrell RT, Olson SH, Sadetzki S, Schildkraut JM, Shete S, Rubin JB, Andersson U, Rajaraman P, Chanock SJ, Linet MS, Wang Z, Yeager M; GliomaScan consortium; Houlston RS, Jenkins RB, Wrensch MR, Melin B, Bondy ML, Barnholtz-Sloan JS. Ostrom QT, et al. Int J Cancer. 2018 Nov 15;143(10):2359-2366. doi: 10.1002/ijc.31759. Epub 2018 Sep 19. Int J Cancer. 2018. PMID: 30152087 Free PMC article.
  • Deciphering the 8q24.21 association for glioma.
    Enciso-Mora V, Hosking FJ, Kinnersley B, Wang Y, Shete S, Zelenika D, Broderick P, Idbaih A, Delattre JY, Hoang-Xuan K, Marie Y, Di Stefano AL, Labussière M, Dobbins S, Boisselier B, Ciccarino P, Rossetto M, Armstrong G, Liu Y, Gousias K, Schramm J, Lau C, Hepworth SJ, Strauch K, Müller-Nurasyid M, Schreiber S, Franke A, Moebus S, Eisele L, Forsti A, Hemminki K, Tomlinson IP, Swerdlow A, Lathrop M, Simon M, Bondy M, Sanson M, Houlston RS. Enciso-Mora V, et al. Hum Mol Genet. 2013 Jun 1;22(11):2293-302. doi: 10.1093/hmg/ddt063. Epub 2013 Feb 11. Hum Mol Genet. 2013. PMID: 23399484 Free PMC article.
  • Australian genome-wide association study confirms higher female risk for adult glioma associated with variants in the region of CCDC26.
    Alpen K, Vajdic CM, MacInnis RJ, Milne RL, Koh ES, Hovey E, Harrup R, Bruinsma F, Nguyen TL, Li S, Joseph D, Benke G, Dugué PA, Southey MC, Giles GG, Rosenthal M, Drummond KJ, Nowak AK, Hopper JL, Kapuscinski M, Makalic E. Alpen K, et al. Neuro Oncol. 2023 Jul 6;25(7):1355-1365. doi: 10.1093/neuonc/noac279. Neuro Oncol. 2023. PMID: 36541697 Free PMC article.
  • Genome-Wide Association Studies in Glioma.
    Kinnersley B, Houlston RS, Bondy ML. Kinnersley B, et al. Cancer Epidemiol Biomarkers Prev. 2018 Apr;27(4):418-428. doi: 10.1158/1055-9965.EPI-17-1080. Epub 2018 Jan 30. Cancer Epidemiol Biomarkers Prev. 2018. PMID: 29382702 Free PMC article. Review.
See all similar articles

Cited by

  • Drug resistance in glioblastoma: from chemo- to immunotherapy.
    Sharma S, Chepurna O, Sun T. Sharma S, et al. Cancer Drug Resist. 2023 Oct 11;6(4):688-708. doi: 10.20517/cdr.2023.82. eCollection 2023. Cancer Drug Resist. 2023. PMID: 38239396 Free PMC article. Review.
  • Sex-Specific Differences in Glioblastoma.
    Carrano A, Juarez JJ, Incontri D, Ibarra A, Guerrero Cazares H. Carrano A, et al. Cells. 2021 Jul 14;10(7):1783. doi: 10.3390/cells10071783. Cells. 2021. PMID: 34359952 Free PMC article. Review.
  • Sex-Specific Differences in Patients with IDH1-Wild-Type Grade 4 Glioma in the ReSPOND Consortium.
    Gongala S, Garcia JA, Korakavi N, Patil N, Akbari H, Sloan A, Barnholtz-Sloan JS, Sun J, Griffith B, Poisson LM, Booth TC, Jain R, Mohan S, Nasralla MP, Bakas S, Tippareddy C, Puig J, Palmer JD, Shi W, Colen RR, Sotiras A, Ahn SS, Park YW, Davatzikos C, Badve C; ReSPOND Consortium. Gongala S, et al. AJNR Am J Neuroradiol. 2024 Sep 9;45(9):1299-1307. doi: 10.3174/ajnr.A8319. AJNR Am J Neuroradiol. 2024. PMID: 38684319
  • Sex-Specific Genetic Associations for Barrett's Esophagus and Esophageal Adenocarcinoma.
    Dong J, Maj C, Tsavachidis S, Ostrom QT, Gharahkhani P, Anderson LA, Wu AH, Ye W, Bernstein L, Borisov O, Schröder J, Chow WH, Gammon MD, Liu G, Caldas C, Pharoah PD, Risch HA, May A, Gerges C, Anders M, Venerito M, Schmidt T, Izbicki JR, Hölscher AH, Schumacher B, Vashist Y, Neuhaus H, Rösch T, Knapp M, Krawitz P, Böhmer A, Iyer PG, Reid BJ, Lagergren J, Shaheen NJ, Corley DA, Gockel I, Fitzgerald RC; Stomach and Oesophageal Cancer Study (SOCS) consortium; Cook MB, Whiteman DC, Vaughan TL, Schumacher J, Thrift AP. Dong J, et al. Gastroenterology. 2020 Dec;159(6):2065-2076.e1. doi: 10.1053/j.gastro.2020.08.052. Epub 2020 Sep 9. Gastroenterology. 2020. PMID: 32918910 Free PMC article.
  • LATS2 inhibits cell proliferation and metastasis through the Hippo signaling pathway in glioma.
    Guo C, Liang C, Yang J, Hu H, Fan B, Liu X. Guo C, et al. Oncol Rep. 2019 May;41(5):2753-2761. doi: 10.3892/or.2019.7065. Epub 2019 Mar 14. Oncol Rep. 2019. PMID: 30896861 Free PMC article.
See all "Cited by" articles

References

    1. Ostrom QT, et al. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2009–2013. Neuro-oncology. 2016;18:v1–v75. doi: 10.1093/neuonc/now207. - DOI - PMC - PubMed
    1. Ostrom QT, et al. The epidemiology of glioma in adults: a “state of the science” review. Neuro-oncology. 2014;16:896–913. doi: 10.1093/neuonc/nou087. - DOI - PMC - PubMed
    1. Kinnersley B, et al. Quantifying the heritability of glioma using genome-wide complex trait analysis. Scientific reports. 2015;5:17267. doi: 10.1038/srep17267. - DOI - PMC - PubMed
    1. Melin BS, et al. Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors. Nature genetics. 2017;49:789–794. doi: 10.1038/ng.3823. - DOI - PMC - PubMed
    1. Benson VS, Kirichek O, Beral V, Green J. Menopausal hormone therapy and central nervous system tumor risk: large UK prospective study and meta-analysis. International journal of cancer. 2015;136:2369–2377. doi: 10.1002/ijc.29274. - DOI - PubMed

Publication types

MeSH terms