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; Dugue, PA; Southey, MC; Giles, GG; Rosenthal, M; Drummond, KJ; Nowak, AK; Hopper, JL; Kapuscinski, M; Makalic, E

Author(s): Alpen, K; Vajdic, CM; MacInnis, RJ; Milne, RL; Koh, ES; Hovey, E; Harrup, R; Bruinsma, F; Nguyen, TL; Li, S; Joseph, D; Benke, G; Dugue, PA; Southey, MC; Giles, GG; Rosenthal, M; Drummond, KJ; Nowak, AK; Hopper, JL; Kapuscinski, M; Makalic, E;
Details: Publication Year 2023-07-06,Volume 25,Issue #7,Page 1355-1365
Journal Title: Neuro-Oncology
Publication Type: Research article
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 analyzed 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 2237 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 2q33.3 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 < .05). We also replicated the previously reported sex difference at 8q24.21 CCDC26 (P = .0024) with the association being nominally significant for both sexes (P < .05). CONCLUSIONS: Our study supports a stronger female risk association for the region 8q24.21 CCDC26 and highlights the importance of analyzing 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.
Publisher: Oxford University Press
Keywords: Female; Humans; Adult; Male; Genome-Wide Association Study; Genetic Predisposition to Disease; Australia; *Glioma/genetics; *Brain Neoplasms/genetics; *Glioblastoma/genetics; Polymorphism, Single Nucleotide; Case-Control Studies; Nerve Tissue Proteins; Intracellular Signaling Peptides and Proteins/genetics; Ccdc26; Gwas; glioblastoma; glioma; sex differences
Department(s): Parkville Cancer Clinical Trials Unit
PubMed ID: 36541697
Publisher's Version: https://doi.org/10.1093/neuonc/noac279
Open Access at Publisher's Site: https://doi.org/10.1093/neuonc/noac279
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-10-17 06:55:46

Last Modified: 2023-10-17 06:58:32