Australian genome-wide association study confirms higher female risk for adult glioma associated with variants in the region of CCDC26

Karen Alpen; Claire M Vajdic; Robert J MacInnis; Roger L Milne; Eng-Siew Koh; Elizabeth Hovey; Rosemary Harrup; Fiona Bruinsma; Tuong L Nguyen; Shuai Li; David Joseph; Geza Benke; Pierre-Antoine Dugué; Melissa C Southey; Graham G Giles; Mark Rosenthal; Katharine J Drummond; Anna K Nowak; John L Hopper; Miroslaw Kapuscinski; Enes Makalic

doi:10.1093/neuonc/noac279

Australian genome-wide association study confirms higher female risk for adult glioma associated with variants in the region of CCDC26

Neuro Oncol. 2023 Jul 6;25(7):1355-1365. doi: 10.1093/neuonc/noac279.

Authors

Karen Alpen¹, Claire M Vajdic², Robert J MacInnis^{1

3}, Roger L Milne^{1

3

4}, Eng-Siew Koh^{5

6

7}, Elizabeth Hovey^{8

9}, Rosemary Harrup^{10

11}, Fiona Bruinsma^{1

3}, Tuong L Nguyen¹, Shuai Li^{1

4

12

13}, David Joseph¹⁴, Geza Benke¹⁵, Pierre-Antoine Dugué^{1

3

4}, Melissa C Southey^{3

4

16}, Graham G Giles^{1

3

4}, Mark Rosenthal¹⁷, Katharine J Drummond^{18

19}, Anna K Nowak²⁰, John L Hopper¹, Miroslaw Kapuscinski¹, Enes Makalic¹

Affiliations

¹ Centre of Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
² The Kirby Institute, UNSW Sydney, Sydney, New South Wales 2052, Australia.
³ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria 3004, Australia.
⁴ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
⁵ South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, New South Wales, Australia.
⁶ Liverpool and Macarthur Cancer Therapy Centres, Liverpool Hospital, Liverpool, New South Wales, Australia.
⁷ Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia.
⁸ Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, Randwick, Sydney, New South Wales 2031, Australia.
⁹ Faculty of Medicine, Prince of Wales Clinical School UNSW, Sydney, New South Wales, 2052, Australia.
¹⁰ Royal Hobart Hospital, Hobart, Tasmania, Australia.
¹¹ University of Tasmania, Hobart, Tasmania, Australia.
¹² Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
¹³ Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria 3051, Australia.
¹⁴ Department of Medicine and Surgery, The University of Western Australia, Perth, Western Australia, Australia.
¹⁵ School of Public Health and Preventative Medicine, Monash University, Clayton, Victoria, 3004, Australia.
¹⁶ Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Parkville, Victoria, Australia.
¹⁷ The Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
¹⁸ Department of Neurosurgery, Royal Melbourne Hospital, Parkville, Victoria, 3050, Australia.
¹⁹ Department of Surgery, University of Melbourne, Parkville, Victoria, 3050, Australia.
²⁰ Medical School, University of Western Australia, Crawley, Western Australia 6008, Australia.

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.

Keywords: CCDC26; GWAS; glioblastoma; glioma; sex differences.

MeSH terms

Adult
Australia
Brain Neoplasms* / genetics
Case-Control Studies
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Glioblastoma* / genetics
Glioma* / genetics
Humans
Intracellular Signaling Peptides and Proteins / genetics
Male
Nerve Tissue Proteins
Polymorphism, Single Nucleotide

Substances

PHLDB1 protein, human
Nerve Tissue Proteins
Intracellular Signaling Peptides and Proteins

Abstract

MeSH terms

Substances

Grants and funding