Abstract
Background
Glioma accounts for approximately 80% of malignant adult brain cancer and its most common subtype, glioblastoma, has one of the lowest 5-year cancer survivals. Fifty risk-associated variants within 34 glioma genetic risk regions have been found by genome-wide association studies (GWAS) with a sex difference reported for 8q24.21 region. We conducted an Australian GWAS by glioma subtype and sex.
Methods
We analysed genome-wide data from the Australian Genomics and Clinical Outcomes of Glioma (AGOG) consortium for 7,573,692 single nucleotide polymorphisms (SNPs) for 560 glioma cases and 2,237 controls of European ancestry. Cases were classified as glioblastoma, non-glioblastoma, astrocytoma or oligodendroglioma Logistic regression analysis was used to assess the associations of SNPs with glioma risk by subtype and by sex.
Results
We replicated the previously reported glioma risk associations in the regions of 2 q33.3
C2orf80, 2q37.3
D2HGDH, 5p15.33
TERT, 7p11.2
EGFR, 8q24.21
CCDC26, 9p21.3
CDKN2BAS, 11q21
MAML2, 11q23.3
PHLDB1, 15q24.2
ETFA, 16p13.3
RHBDF1, 16p13.3
LMF1, 17p13.1
TP53, 20q13.33
RTEL and 20q13.33
GMEB2 (
P<0.05). We also replicated the previously reported sex difference at 8q24.21
CCDC26 (P=0.0024) with the association being nominally significan t for both sexes (P<0.05).
Conclusions
Our study supports a stronger female risk association for the region 8q24.21
CCDC26 and highlights the importance of analysing glioma GWAS by sex. A better understanding of sex differences could provide biological insight into the cause of glioma with implications for prevention, risk prediction and treatment.
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