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Using germline variants to estimate glioma and subtype risks
- Source :
- Neuro-oncology, vol 21, iss 4
- Publication Year :
- 2019
- Publisher :
- Oxford University Press (OUP), 2019.
-
Abstract
- BACKGROUND: Twenty-five single nucleotide polymorphisms (SNPs) are associated with adult diffuse glioma risk. We hypothesized that the inclusion of these 25 SNPs with age at diagnosis and sex could estimate risk of glioma as well as identify glioma subtypes. METHODS: Case-control design and multinomial logistic regression were used to develop models to estimate the risk of glioma development while accounting for histologic and molecular subtypes. Case-case design and logistic regression were used to develop models to predict isocitrate dehydrogenase (IDH) mutation status. A total of 1273 glioma cases and 443 controls from Mayo Clinic were used in the discovery set, and 852 glioma cases and 231 controls from UCSF were used in the validation set. All samples were genotyped using a custom Illumina OncoArray. RESULTS: Patients in the highest 5% of the risk score had more than a 14-fold increase in relative risk of developing an IDH mutant glioma. Large differences in lifetime absolute risk were observed at the extremes of the risk score percentile. For both IDH mutant 1p/19q non-codeleted glioma and IDH mutant 1p/19q codeleted glioma, the lifetime risk increased from almost null to 2.3% and almost null to 1.7%, respectively. The SNP-based model that predicted IDH mutation status had a validation concordance index of 0.85. CONCLUSIONS: These results suggest that germline genotyping can provide new tools for the initial management of newly discovered brain lesions. Given the low lifetime risk of glioma, risk scores will not be useful for population screening; however, they may be useful in certain clinically defined high-risk groups.
- Subjects :
- Male
Cancer Research
genotype
Age at diagnosis
polygenic
Germline
Diffuse Glioma
0302 clinical medicine
Risk Factors
glioma
Genotype
80 and over
Cancer
Aged, 80 and over
Brain Neoplasms
Single Nucleotide
Middle Aged
classification
Oncology
030220 oncology & carcinogenesis
Basic and Translational Investigations
Female
Adult
Adolescent
Oncology and Carcinogenesis
Single-nucleotide polymorphism
Biology
Polymorphism, Single Nucleotide
Young Adult
03 medical and health sciences
Rare Diseases
Clinical Research
Glioma
Genetics
medicine
Humans
Oncology & Carcinogenesis
Polymorphism
Aged
glioblastoma
Neurosciences
medicine.disease
Brain Disorders
Brain Cancer
Case-Control Studies
Cancer research
Neurology (clinical)
030217 neurology & neurosurgery
Glioblastoma
Subjects
Details
- ISSN :
- 15235866 and 15228517
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Neuro-Oncology
- Accession number :
- edsair.doi.dedup.....7b0364f75c35facb03345e92a4010256