Inherited variant on chromosome 11q23 increases susceptibility to IDH-mutated but not IDH-normal gliomas regardless of grade or histology
Copyright policy )Inherited variant on chromosome 11q23 increases susceptibility to IDH-mutated but not IDH-normal gliomas regardless of grade or histology
Recent discoveries of inherited glioma risk loci and acquired IDH mutations are providing new insights into glioma etiology. IDH mutations are common in lower grade gliomas and secondary glioblastomas and uncommon in primary glioblastomas. Because the inherited variant in 11q23 has been associated with risk of lower grade glioma and not with glioblastomas, we hypothesized that this variant increases susceptibility to IDH-mutated gliomas, but not to IDH-wild-type gliomas.We tested this hypothesis in patients with glioma and controls from the San Francisco Adult Glioma Study, the Mayo Clinic, and Illumina controls (1102 total patients, 5299 total controls). Case-control additive associations of 11q23 risk alleles (rs498872, T allele) were calculated using logistic regression, stratified by tumor IDH status (mutated or wild-type) and by histology and grade. We also adjusted for the recently discovered 8q24 glioma risk locus rs55705857 G allele.The 11q23 glioma risk locus was associated with increased risk of IDH-mutated gliomas of all histologies and grades (odds ratio [OR] = 1.50; 95% confidence interval [CI] = 1.29-1.74; P = 1.3X10(-7)) but not with IDH-wild-type gliomas of any histology or grade (OR = 0.91; 95% CI = 0.81-1.03; P = 0.14). The associations were independent of the rs55705857 G allele.A variant at the 11q23 locus increases risk for IDH-mutated but not IDH-wild-type gliomas, regardless of grade or histology.
- Mayo Clinic United States
- Gladstone Institutes United States
- University of California, San Francisco United States
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Male, Pair 11 (mesh), rs55705857, Neoplasm Grading (mesh), Clinical Research (rcdc), Pair 8 (mesh), adult glioma, Brain Disorders (rcdc), Glioma (mesh), 2.1 Biological and endogenous factors, Pair 11, 32 Biomedical and Clinical Sciences (for-2020), Male (mesh), Neurosciences (rcdc), Genetic Predisposition to Disease (mesh), Cancer, Cancer (rcdc), Brain Cancer (rcdc), Humans (mesh), Tumor, Mutation (mesh), Brain Neoplasms, Single Nucleotide, Glioma, single-nucleotide polymorphism, 1112 Oncology and Carcinogenesis (for), Middle Aged, Isocitrate Dehydrogenase (mesh), Prognosis, Isocitrate Dehydrogenase, rs498872, Pair 8, Female, Tumor (mesh), Brain Neoplasms (mesh), Human, Chromosomes, Human, Pair 8, Adult, Single Nucleotide (mesh), IDH1 and IDH2 mutation, Clinical Sciences, Oncology and Carcinogenesis, 610, Polymorphism, Single Nucleotide, Case-Control Studies (mesh), Chromosomes, Rare Diseases (rcdc), Rare Diseases, Clinical Research, Middle Aged (mesh), Genetics, Biomarkers, Tumor, 3211 Oncology and carcinogenesis (for-2020), Humans, Genetic Predisposition to Disease, Oncology & Carcinogenesis, Polymorphism, 3202 Clinical Sciences (for-2020), Neoplasm Staging, Biomedical and Clinical Sciences, Genetics (rcdc), Chromosomes, Human, Pair 11, Neurosciences, 2.1 Biological and endogenous factors (hrcs-rac), Prognosis (mesh), 1109 Neurosciences (for), Brain Disorders, Brain Cancer, Neoplasm Staging (mesh), 3211 Oncology and Carcinogenesis (for-2020), Oncology & Carcinogenesis (science-metrix), Female (mesh), Case-Control Studies, Mutation, Adult (mesh), Neoplasm Grading, Biomarkers
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