199 results on '"Lachance, Daniel H."'
Search Results
2. A noncoding single-nucleotide polymorphism at 8q24 drives IDH1-mutant glioma formation
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Yanchus, Connor, Drucker, Kristen L, Kollmeyer, Thomas M, Tsai, Ricky, Winick-Ng, Warren, Liang, Minggao, Malik, Ahmad, Pawling, Judy, De Lorenzo, Silvana B, Ali, Asma, Decker, Paul A, Kosel, Matt L, Panda, Arijit, Al-Zahrani, Khalid N, Jiang, Lingyan, Browning, Jared WL, Lowden, Chris, Geuenich, Michael, Hernandez, J Javier, Gosio, Jessica T, Ahmed, Musaddeque, Loganathan, Sampath Kumar, Berman, Jacob, Trcka, Daniel, Michealraj, Kulandaimanuvel Antony, Fortin, Jerome, Carson, Brittany, Hollingsworth, Ethan W, Jacinto, Sandra, Mazrooei, Parisa, Zhou, Lily, Elia, Andrew, Lupien, Mathieu, He, Housheng Hansen, Murphy, Daniel J, Wang, Liguo, Abyzov, Alexej, Dennis, James W, Maass, Philipp G, Campbell, Kieran, Wilson, Michael D, Lachance, Daniel H, Wrensch, Margaret, Wiencke, John, Mak, Tak, Pennacchio, Len A, Dickel, Diane E, Visel, Axel, Wrana, Jeffrey, Taylor, Michael D, Zadeh, Gelareh, Dirks, Peter, Eckel-Passow, Jeanette E, Attisano, Liliana, Pombo, Ana, Ida, Cristiane M, Kvon, Evgeny Z, Jenkins, Robert B, and Schramek, Daniel
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Brain Cancer ,Brain Disorders ,Human Genome ,Neurosciences ,Rare Diseases ,Genetics ,Cancer Genomics ,Cancer ,2.1 Biological and endogenous factors ,Animals ,Brain Neoplasms ,Chromosomes ,Human ,Pair 8 ,Glioma ,Humans ,Isocitrate Dehydrogenase ,Mice ,Mutation ,Polymorphism ,Single Nucleotide ,General Science & Technology - Abstract
Establishing causal links between inherited polymorphisms and cancer risk is challenging. Here, we focus on the single-nucleotide polymorphism rs55705857, which confers a sixfold greater risk of isocitrate dehydrogenase (IDH)-mutant low-grade glioma (LGG). We reveal that rs55705857 itself is the causal variant and is associated with molecular pathways that drive LGG. Mechanistically, we show that rs55705857 resides within a brain-specific enhancer, where the risk allele disrupts OCT2/4 binding, allowing increased interaction with the Myc promoter and increased Myc expression. Mutating the orthologous mouse rs55705857 locus accelerated tumor development in an Idh1R132H-driven LGG mouse model from 472 to 172 days and increased penetrance from 30% to 75%. Our work reveals mechanisms of the heritable predisposition to lethal glioma in ~40% of LGG patients.
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- 2022
3. Adult diffuse glioma GWAS by molecular subtype identifies variants in D2HGDH and FAM20C
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Eckel-Passow, Jeanette E, Drucker, Kristen L, Kollmeyer, Thomas M, Kosel, Matt L, Decker, Paul A, Molinaro, Annette M, Rice, Terri, Praska, Corinne E, Clark, Lauren, Caron, Alissa, Abyzov, Alexej, Batzler, Anthony, Song, Jun S, Pekmezci, Melike, Hansen, Helen M, McCoy, Lucie S, Bracci, Paige M, Wiemels, Joseph, Wiencke, John K, Francis, Stephen, Burns, Terry C, Giannini, Caterina, Lachance, Daniel H, Wrensch, Margaret, and Jenkins, Robert B
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Neurosciences ,Brain Disorders ,Cancer Genomics ,Cancer ,Brain Cancer ,Genetics ,Rare Diseases ,Human Genome ,2.1 Biological and endogenous factors ,Adult ,Alcohol Oxidoreductases ,Brain Neoplasms ,Casein Kinase I ,Extracellular Matrix Proteins ,Female ,Genome-Wide Association Study ,Glioma ,Humans ,Isocitrate Dehydrogenase ,Male ,Middle Aged ,Mutation ,Telomerase ,allergy ,glioblastoma ,GWAS glioma ,molecular subtype ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundTwenty-five germline variants are associated with adult diffuse glioma, and some of these variants have been shown to be associated with particular subtypes of glioma. We hypothesized that additional germline variants could be identified if a genome-wide association study (GWAS) were performed by molecular subtype.MethodsA total of 1320 glioma cases and 1889 controls were used in the discovery set and 799 glioma cases and 808 controls in the validation set. Glioma cases were classified into molecular subtypes based on combinations of isocitrate dehydrogenase (IDH) mutation, telomerase reverse transcriptase (TERT) promoter mutation, and 1p/19q codeletion. Logistic regression was applied to the discovery and validation sets to test for associations of variants with each of the subtypes. A meta-analysis was subsequently performed using a genome-wide P-value threshold of 5 × 10-8.ResultsNine variants in or near D-2-hydroxyglutarate dehydrogenase (D2HGDH) on chromosome 2 were genome-wide significant in IDH-mutated glioma (most significant was rs5839764, meta P = 2.82 × 10-10). Further stratifying by 1p/19q codeletion status, one variant in D2HGDH was genome-wide significant in IDH-mutated non-codeleted glioma (rs1106639, meta P = 4.96 × 10-8). Further stratifying by TERT mutation, one variant near FAM20C (family with sequence similarity 20, member C) on chromosome 7 was genome-wide significant in gliomas that have IDH mutation, TERT mutation, and 1p/19q codeletion (rs111976262, meta P = 9.56 × 10-9). Thirty-six variants in or near GMEB2 on chromosome 20 near regulator of telomere elongation helicase 1 (RTEL1) were genome-wide significant in IDH wild-type glioma (most significant was rs4809313, meta P = 2.60 × 10-10).ConclusionsPerforming a GWAS by molecular subtype identified 2 new regions and a candidate independent region near RTEL1, which were associated with specific glioma molecular subtypes.
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- 2020
4. Glioma risk associated with extent of estimated European genetic ancestry in African Americans and Hispanics
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Ostrom, Quinn T, Egan, Kathleen M, Nabors, L Burt, Gerke, Travis, Thompson, Reid C, Olson, Jeffrey J, LaRocca, Renato, Chowdhary, Sajeel, Eckel‐Passow, Jeanette E, Armstrong, Georgina, Wiencke, John K, Bernstein, Jonine L, Claus, Elizabeth B, Il'yasova, Dora, Johansen, Christoffer, Lachance, Daniel H, Lai, Rose K, Merrell, Ryan T, Olson, Sara H, Sadetzki, Siegal, Schildkraut, Joellen M, Shete, Sanjay, Houlston, Richard S, Jenkins, Robert B, Wrensch, Margaret R, Melin, Beatrice, Amos, Christopher I, Huse, Jason T, Barnholtz‐Sloan, Jill S, and Bondy, Melissa L
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Human Genome ,Neurosciences ,Rare Diseases ,Brain Disorders ,Genetics ,Black or African American ,Case-Control Studies ,Female ,Genetic Association Studies ,Genetic Loci ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genotype ,Glioma ,Hispanic or Latino ,Humans ,Male ,Middle Aged ,Polymorphism ,Single Nucleotide ,Risk ,White People ,glioma ,genetic epidemiology ,genetic ancestry ,genome-wide association study ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
Glioma incidence is highest in non-Hispanic Whites, and to date, glioma genome-wide association studies (GWAS) to date have only included European ancestry (EA) populations. African Americans and Hispanics in the US have varying proportions of EA, African (AA) and Native American ancestries (NAA). It is unknown if identified GWAS loci or increased EA is associated with increased glioma risk. We assessed whether EA was associated with glioma in African Americans and Hispanics. Data were obtained for 832 cases and 675 controls from the Glioma International Case-Control Study and GliomaSE Case-Control Study previously estimated to have
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- 2020
5. Using germline variants to estimate glioma and subtype risks
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Eckel-Passow, Jeanette E, Decker, Paul A, Kosel, Matt L, Kollmeyer, Thomas M, Molinaro, Annette M, Rice, Terri, Caron, Alissa A, Drucker, Kristen L, Praska, Corinne E, Pekmezci, Melike, Hansen, Helen M, McCoy, Lucie S, Bracci, Paige M, Erickson, Bradley J, Lucchinetti, Claudia F, Wiemels, Joseph L, Wiencke, John K, Bondy, Melissa L, Melin, Beatrice, Burns, Terry C, Giannini, Caterina, Lachance, Daniel H, Wrensch, Margaret R, and Jenkins, Robert B
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Genetics ,Brain Disorders ,Cancer ,Clinical Research ,Neurosciences ,Brain Cancer ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Brain Neoplasms ,Case-Control Studies ,Female ,Genotype ,Glioma ,Humans ,Male ,Middle Aged ,Polymorphism ,Single Nucleotide ,Risk Factors ,Young Adult ,classification ,genotype ,glioblastoma ,glioma ,polygenic ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundTwenty-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.MethodsCase-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.ResultsPatients 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.ConclusionsThese 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.
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- 2019
6. Age‐specific genome‐wide association study in glioblastoma identifies increased proportion of ‘lower grade glioma’‐like features associated with younger age
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Ostrom, Quinn T, Kinnersley, Ben, Armstrong, Georgina, Rice, Terri, Chen, Yanwen, Wiencke, John K, McCoy, Lucie S, Hansen, Helen M, Amos, Christopher I, Bernstein, Jonine L, Claus, Elizabeth B, Eckel‐Passow, Jeanette E, Il'yasova, Dora, Johansen, Christoffer, Lachance, Daniel H, Lai, Rose K, Merrell, Ryan T, Olson, Sara H, Sadetzki, Siegal, Schildkraut, Joellen M, Shete, Sanjay, Rubin, Joshua B, Andersson, Ulrika, Rajaraman, Preetha, Chanock, Stephen J, Linet, Martha S, Wang, Zhaoming, Yeager, Meredith, consortium, on behalf of the GliomaScan, Houlston, Richard S, Jenkins, Robert B, Wrensch, Margaret R, Melin, Beatrice, Bondy, Melissa L, and Barnholtz‐Sloan, Jill S
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Brain Cancer ,Rare Diseases ,Neurosciences ,Brain Disorders ,Genetics ,Cancer ,Human Genome ,Adolescent ,Adult ,Age Factors ,Aged ,Brain Neoplasms ,Case-Control Studies ,Female ,Genome-Wide Association Study ,Glioblastoma ,Humans ,Male ,Middle Aged ,Neoplasm Grading ,Polymorphism ,Single Nucleotide ,Young Adult ,glioma ,brain tumors ,age ,GliomaScan consortium ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
Glioblastoma (GBM) is the most common malignant brain tumor in the United States. Incidence of GBM increases with age, and younger age-at-diagnosis is significantly associated with improved prognosis. While the relationship between candidate GBM risk SNPs and age-at-diagnosis has been explored, genome-wide association studies (GWAS) have not previously been stratified by age. Potential age-specific genetic effects were assessed in autosomal SNPs for GBM patients using data from four previous GWAS. Using age distribution tertiles (18-53, 54-64, 65+) datasets were analyzed using age-stratified logistic regression to generate p values, odds ratios (OR), and 95% confidence intervals (95%CI), and then combined using meta-analysis. There were 4,512 total GBM cases, and 10,582 controls used for analysis. Significant associations were detected at two previously identified SNPs in 7p11.2 (rs723527 [p54-63 = 1.50x10-9 , OR54-63 = 1.28, 95%CI54-63 = 1.18-1.39; p64+ = 2.14x10-11 , OR64+ = 1.32, 95%CI64+ = 1.21-1.43] and rs11979158 [p54-63 = 6.13x10-8 , OR54-63 = 1.35, 95%CI54-63 = 1.21-1.50; p64+ = 2.18x10-10 , OR64+ = 1.42, 95%CI64+ = 1.27-1.58]) but only in persons >54. There was also a significant association at the previously identified lower grade glioma (LGG) risk locus at 8q24.21 (rs55705857) in persons ages 18-53 (p18-53 = 9.30 × 10-11 , OR18-53 = 1.76, 95%CI18-53 = 1.49-2.10). Within The Cancer Genome Atlas (TCGA) there was higher prevalence of 'LGG'-like tumor characteristics in GBM samples in those 18-53, with IDH1/2 mutation frequency of 15%, as compared to 2.1% [54-63] and 0.8% [64+] (p = 0.0005). Age-specific differences in cancer susceptibility can provide important clues to etiology. The association of a SNP known to confer risk for IDH1/2 mutant glioma and higher prevalence of IDH1/2 mutation within younger individuals 18-53 suggests that more younger individuals may present initially with 'secondary glioblastoma.'
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- 2018
7. Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21.
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Ostrom, Quinn T, Kinnersley, Ben, Wrensch, Margaret R, Eckel-Passow, Jeanette E, Armstrong, Georgina, Rice, Terri, Chen, Yanwen, Wiencke, John K, McCoy, Lucie S, Hansen, Helen M, Amos, Christopher I, Bernstein, Jonine L, Claus, Elizabeth B, Il'yasova, Dora, Johansen, Christoffer, Lachance, Daniel H, Lai, Rose K, Merrell, Ryan T, Olson, Sara H, Sadetzki, Siegal, Schildkraut, Joellen M, Shete, Sanjay, Rubin, Joshua B, Lathia, Justin D, Berens, Michael E, Andersson, Ulrika, Rajaraman, Preetha, Chanock, Stephen J, Linet, Martha S, Wang, Zhaoming, Yeager, Meredith, GliomaScan consortium, Houlston, Richard S, Jenkins, Robert B, Melin, Beatrice, Bondy, Melissa L, and Barnholtz-Sloan, Jill S
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GliomaScan consortium ,Chromosomes ,Human ,Pair 3 ,Chromosomes ,Human ,Pair 7 ,Chromosomes ,Human ,Pair 8 ,Humans ,Glioma ,Brain Neoplasms ,Genetic Predisposition to Disease ,Logistic Models ,Odds Ratio ,Risk Factors ,Case-Control Studies ,Sex Factors ,Genotype ,Polymorphism ,Single Nucleotide ,Alleles ,Adult ,Middle Aged ,Female ,Male ,Genome-Wide Association Study ,Neurosciences ,Human Genome ,Genetics ,Prevention ,Rare Diseases ,Brain Cancer ,Cancer ,Brain Disorders - Abstract
Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.
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- 2018
8. Clinical manifestations of, diagnostic approach to, and treatment of neurolymphomatosis in the rituximab era
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Khurana, Arushi, Novo, Mattia, Nowakowski, Grzegorz S., Ristow, Kay M., Spinner, Robert J., Hunt, Christopher H., King, Rebecca L., Lachance, Daniel H., Habermann, Thomas M., Micallef, Ivana N., and Johnston, Patrick B.
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- 2021
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9. Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT
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Pekmezci, Melike, Rice, Terri, Molinaro, Annette M, Walsh, Kyle M, Decker, Paul A, Hansen, Helen, Sicotte, Hugues, Kollmeyer, Thomas M, McCoy, Lucie S, Sarkar, Gobinda, Perry, Arie, Giannini, Caterina, Tihan, Tarik, Berger, Mitchel S, Wiemels, Joseph L, Bracci, Paige M, Eckel-Passow, Jeanette E, Lachance, Daniel H, Clarke, Jennifer, Taylor, Jennie W, Luks, Tracy, Wiencke, John K, Jenkins, Robert B, and Wrensch, Margaret R
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Brain Disorders ,Genetics ,Neurosciences ,Cancer Genomics ,Brain Cancer ,Human Genome ,Cancer ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Biomarkers ,Tumor ,Case-Control Studies ,Central Nervous System Neoplasms ,Female ,Glioma ,Humans ,Isocitrate Dehydrogenase ,Kaplan-Meier Estimate ,Male ,Middle Aged ,Mutation ,Neoplasm Grading ,Prognosis ,Telomerase ,World Health Organization ,X-linked Nuclear Protein ,Young Adult ,Glioma classification ,ATRX alteration ,TERT promoter mutation ,Brain tumor prognosis ,Telomere maintenance ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
The "integrated diagnosis" for infiltrating gliomas in the 2016 revised World Health Organization (WHO) classification of tumors of the central nervous system requires assessment of the tumor for IDH mutations and 1p/19q codeletion. Since TERT promoter mutations and ATRX alterations have been shown to be associated with prognosis, we analyzed whether these tumor markers provide additional prognostic information within each of the five WHO 2016 categories. We used data for 1206 patients from the UCSF Adult Glioma Study, the Mayo Clinic and The Cancer Genome Atlas (TCGA) with infiltrative glioma, grades II-IV for whom tumor status for IDH, 1p/19q codeletion, ATRX, and TERT had been determined. All cases were assigned to one of 5 groups following the WHO 2016 diagnostic criteria based on their morphologic features, and IDH and 1p/19q codeletion status. These groups are: (1) Oligodendroglioma, IDH-mutant and 1p/19q-codeleted; (2) Astrocytoma, IDH-mutant; (3) Glioblastoma, IDH-mutant; (4) Glioblastoma, IDH-wildtype; and (5) Astrocytoma, IDH-wildtype. Within each group, we used univariate and multivariate Cox proportional hazards models to assess associations of overall survival with patient age at diagnosis, grade, and ATRX alteration status and/or TERT promoter mutation status. Among Group 1 IDH-mutant 1p/19q-codeleted oligodendrogliomas, the TERT-WT group had significantly worse overall survival than the TERT-MUT group (HR: 2.72, 95% CI 1.05-7.04, p = 0.04). In both Group 2, IDH-mutant astrocytomas and Group 3, IDH-mutant glioblastomas, neither TERT mutations nor ATRX alterations were significantly associated with survival. Among Group 4, IDH-wildtype glioblastomas, ATRX alterations were associated with favorable outcomes (HR: 0.36, 95% CI 0.17-0.81, p = 0.01). Among Group 5, IDH-wildtype astrocytomas, the TERT-WT group had significantly better overall survival than the TERT-MUT group (HR: 0.48, 95% CI 0.27-0.87), p = 0.02). Thus, we present evidence that in certain WHO 2016 diagnostic groups, testing for TERT promoter mutations or ATRX alterations may provide additional useful prognostic information.
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- 2017
10. Understanding inherited genetic risk of adult glioma – a review
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Rice, Terri, Lachance, Daniel H, Molinaro, Annette M, Eckel-Passow, Jeanette E, Walsh, Kyle M, Barnholtz-Sloan, Jill, Ostrom, Quinn T, Francis, Stephen S, Wiemels, Joseph, Jenkins, Robert B, Wiencke, John K, and Wrensch, Margaret R
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Brain Disorders ,Brain Cancer ,Cancer ,Genetics ,Human Genome ,Genetic Testing ,Neurosciences ,Rare Diseases ,2.1 Biological and endogenous factors ,epidemiology ,genetics ,primary adult glioma ,risk ,variants ,Oncology and carcinogenesis - Abstract
During the past six years, researchers have made major progress identifying common inherited genetic variation that increases risk for primary adult glioma. This paper summarizes knowledge about rare familial cancer syndromes that include adult glioma and reviews the available literature on the more recently discovered common inherited variation. Ten independent inherited variants in eight chromosomal regions have been convincingly associated with increased risk for adult glioma. Most of these variants increase relative risk of primary adult glioma by 20% to 40%, but the TP53 variant rs78378222 confers a two-fold relative risk (ie, 200%), and rs557505857 on chromosome 8 confers a six-fold relative risk of IDH-mutated astrocytomas and oligodendroglial tumors (ie, 600%). Even with a six-fold relative risk, the overall risk of developing adult glioma is too low for screening for the high-risk variant on chromosome 8. Future studies will help clarify which inherited adult glioma risk variants are associated with subtypes defined by histology and/or acquired tumor mutations. This review also provides an information sheet for primary adult glioma patients and their families.
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- 2016
11. A Heritable Missense Polymorphism in CDKN2A Confers Strong Risk of Childhood Acute Lymphoblastic Leukemia and Is Preferentially Selected during Clonal Evolution
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Walsh, Kyle M, de Smith, Adam J, Hansen, Helen M, Smirnov, Ivan V, Gonseth, Semira, Endicott, Alyson A, Xiao, Jianqiao, Rice, Terri, Fu, Cecilia H, McCoy, Lucie S, Lachance, Daniel H, Eckel-Passow, Jeanette E, Wiencke, John K, Jenkins, Robert B, Wrensch, Margaret R, Ma, Xiaomei, Metayer, Catherine, and Wiemels, Joseph L
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Biological Sciences ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Genetics ,Pediatric Cancer ,Rare Diseases ,Brain Disorders ,Clinical Research ,Hematology ,Human Genome ,Cancer ,Pediatric ,Brain Cancer ,Childhood Leukemia ,Aetiology ,2.1 Biological and endogenous factors ,Case-Control Studies ,Child ,Evolution ,Molecular ,Female ,Genes ,p16 ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genotype ,Humans ,Male ,Polymorphism ,Single Nucleotide ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Oncology & Carcinogenesis ,Biochemistry and cell biology ,Oncology and carcinogenesis - Abstract
Genome-wide association studies (GWAS) have identified SNPs in six genes that are associated with childhood acute lymphoblastic leukemia (ALL). A lead SNP was found to occur on chromosome 9p21.3, a region that is deleted in 30% of childhood ALLs, suggesting the presence of causal polymorphisms linked to ALL risk. We used SNP genotyping and imputation-based fine-mapping of a multiethnic ALL case-control population (Ncases = 1,464, Ncontrols = 3,279) to identify variants of large effect within 9p21.3. We identified a CDKN2A missense variant (rs3731249) with 2% allele frequency in controls that confers three-fold increased risk of ALL in children of European ancestry (OR, 2.99; P = 1.51 × 10(-9)) and Hispanic children (OR, 2.77; P = 3.78 × 10(-4)). Moreover, of 17 patients whose tumors displayed allelic imbalance at CDKN2A, 14 preferentially retained the risk allele and lost the protective allele (PBinomial = 0.006), suggesting that the risk allele provides a selective advantage during tumor growth. Notably, the CDKN2A variant was not significantly associated with melanoma, glioblastoma, or pancreatic cancer risk, implying that this polymorphism specifically confers ALL risk but not general cancer risk. Taken together, our findings demonstrate that coding polymorphisms of large effect can underlie GWAS "hits" and that inherited polymorphisms may undergo directional selection during clonal expansion of tumors.
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- 2015
12. Telomere maintenance and the etiology of adult glioma
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Walsh, Kyle M, Wiencke, John K, Lachance, Daniel H, Wiemels, Joseph L, Molinaro, Annette M, Eckel-Passow, Jeanette E, Jenkins, Robert B, and Wrensch, Margaret R
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Aging ,Rare Diseases ,Neurosciences ,Cancer ,Brain Cancer ,Genetics ,Clinical Research ,Prevention ,Human Genome ,Brain Disorders ,Aetiology ,2.1 Biological and endogenous factors ,Adult ,Brain Neoplasms ,Glioma ,Humans ,Telomere ,genome-wide association ,glioma ,shelterin ,telomerase ,telomere ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
A growing body of epidemiologic and tumor genomic research has identified an important role for telomere maintenance in glioma susceptibility, initiation, and prognosis. Telomere length has long been investigated in relation to cancer, but whether longer or shorter telomere length might be associated with glioma risk has remained elusive. Recent data address this question and are reviewed here. Common inherited variants near the telomerase-component genes TERC and TERT are associated both with longer telomere length and increased risk of glioma. Exome sequencing of glioma patients from families with multiple affected members has identified rare inherited mutations in POT1 (protection of telomeres protein 1) as high-penetrance glioma risk factors. These heritable POT1 mutations are also associated with increased telomere length in leukocytes. Tumor sequencing studies further indicate that acquired somatic mutations of TERT and ATRX are among the most frequent alterations found in adult gliomas. These mutations facilitate telomere lengthening, thus bypassing a critical mechanism of apoptosis. Although future research is needed, mounting evidence suggests that glioma is, at least in part, a disease of telomere dysregulation. Specifically, several inherited and acquired variants underlying gliomagenesis affect telomere pathways and are also associated with increased telomere length.
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- 2015
13. Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors
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Eckel-Passow, Jeanette E, Lachance, Daniel H, Molinaro, Annette M, Walsh, Kyle M, Decker, Paul A, Sicotte, Hugues, Pekmezci, Melike, Rice, Terri, Kosel, Matt L, Smirnov, Ivan V, Sarkar, Gobinda, Caron, Alissa A, Kollmeyer, Thomas M, Praska, Corinne E, Chada, Anisha R, Halder, Chandralekha, Hansen, Helen M, McCoy, Lucie S, Bracci, Paige M, Marshall, Roxanne, Zheng, Shichun, Reis, Gerald F, Pico, Alexander R, O'Neill, Brian P, Buckner, Jan C, Giannini, Caterina, Huse, Jason T, Perry, Arie, Tihan, Tarik, Berger, Mitchell S, Chang, Susan M, Prados, Michael D, Wiemels, Joseph, Wiencke, John K, Wrensch, Margaret R, and Jenkins, Robert B
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Brain Disorders ,Orphan Drug ,Brain Cancer ,Rare Diseases ,Clinical Research ,Neurosciences ,Cancer ,Genetics ,Adult ,Age of Onset ,Biomarkers ,Tumor ,Chromosomes ,Human ,Pair 1 ,Chromosomes ,Human ,Pair 19 ,DNA Mutational Analysis ,DNA ,Neoplasm ,Female ,Germ-Line Mutation ,Glioma ,Humans ,Isocitrate Dehydrogenase ,Kaplan-Meier Estimate ,Male ,Middle Aged ,Mutation ,Neoplasm Grading ,Promoter Regions ,Genetic ,Proportional Hazards Models ,Telomerase ,Medical and Health Sciences ,General & Internal Medicine ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundThe prediction of clinical behavior, response to therapy, and outcome of infiltrative glioma is challenging. On the basis of previous studies of tumor biology, we defined five glioma molecular groups with the use of three alterations: mutations in the TERT promoter, mutations in IDH, and codeletion of chromosome arms 1p and 19q (1p/19q codeletion). We tested the hypothesis that within groups based on these features, tumors would have similar clinical variables, acquired somatic alterations, and germline variants.MethodsWe scored tumors as negative or positive for each of these markers in 1087 gliomas and compared acquired alterations and patient characteristics among the five primary molecular groups. Using 11,590 controls, we assessed associations between these groups and known glioma germline variants.ResultsAmong 615 grade II or III gliomas, 29% had all three alterations (i.e., were triple-positive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only TERT mutations; 5% had other combinations. Among 472 grade IV gliomas, less than 1% were triple-positive, 2% had TERT and IDH mutations, 7% had only IDH mutations, 17% were triple-negative, and 74% had only TERT mutations. The mean age at diagnosis was lowest (37 years) among patients who had gliomas with only IDH mutations and was highest (59 years) among patients who had gliomas with only TERT mutations. The molecular groups were independently associated with overall survival among patients with grade II or III gliomas but not among patients with grade IV gliomas. The molecular groups were associated with specific germline variants.ConclusionsGliomas were classified into five principal groups on the basis of three tumor markers. The groups had different ages at onset, overall survival, and associations with germline variants, which implies that they are characterized by distinct mechanisms of pathogenesis. (Funded by the National Institutes of Health and others.).
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- 2015
14. Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk
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Walsh, Kyle M, Codd, Veryan, Smirnov, Ivan V, Rice, Terri, Decker, Paul A, Hansen, Helen M, Kollmeyer, Thomas, Kosel, Matthew L, Molinaro, Annette M, McCoy, Lucie S, Bracci, Paige M, Cabriga, Belinda S, Pekmezci, Melike, Zheng, Shichun, Wiemels, Joseph L, Pico, Alexander R, Tihan, Tarik, Berger, Mitchell S, Chang, Susan M, Prados, Michael D, Lachance, Daniel H, O'Neill, Brian Patrick, Sicotte, Hugues, Eckel-Passow, Jeanette E, van der Harst, Pim, Wiencke, John K, Samani, Nilesh J, Jenkins, Robert B, and Wrensch, Margaret R
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Agricultural ,Veterinary and Food Sciences ,Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,Agricultural Biotechnology ,Cancer ,Neurosciences ,Brain Disorders ,Brain Cancer ,Rare Diseases ,Prevention ,Adult ,Case-Control Studies ,Genome-Wide Association Study ,Genotype ,Glioma ,Humans ,Leukocytes ,Neoplasm Grading ,Polymorphism ,Single Nucleotide ,Prognosis ,RNA ,Risk Factors ,Telomerase ,Telomere ,ENGAGE Consortium Telomere Group ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Glioma, the most common central nervous system cancer in adults, has poor prognosis. Here we identify a new SNP associated with glioma risk, rs1920116 (near TERC), that reached genome-wide significance (Pcombined = 8.3 × 10(-9)) in a meta-analysis of genome-wide association studies (GWAS) of high-grade glioma and replication data (1,644 cases and 7,736 controls). This region has previously been associated with mean leukocyte telomere length (LTL). We therefore examined the relationship between LTL and both this new risk locus and other previously established risk loci for glioma using data from a recent GWAS of LTL (n = 37,684 individuals). Alleles associated with glioma risk near TERC and TERT were strongly associated with longer LTL (P = 5.5 × 10(-20) and 4.4 × 10(-19), respectively). In contrast, risk-associated alleles near RTEL1 were inconsistently associated with LTL, suggesting the presence of distinct causal alleles. No other risk loci for glioma were associated with LTL. The identification of risk alleles for glioma near TERC and TERT that also associate with telomere length implicates telomerase in gliomagenesis.
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- 2014
15. Genetic variants in telomerase-related genes are associated with an older age at diagnosis in glioma patients: evidence for distinct pathways of gliomagenesis
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Walsh, Kyle M, Rice, Terri, Decker, Paul A, Kosel, Matthew L, Kollmeyer, Thomas, Hansen, Helen M, Zheng, Shichun, McCoy, Lucie S, Bracci, Paige M, Anderson, Erik, Hsuang, George, Wiemels, Joe L, Pico, Alexander R, Smirnov, Ivan, Molinaro, Annette M, Tihan, Tarik, Berger, Mitchell S, Chang, Susan M, Prados, Michael D, Lachance, Daniel H, Sicotte, Hugues, Eckel-Passow, Jeanette E, Wiencke, John K, Jenkins, Robert B, and Wrensch, Margaret R
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Prevention ,Neurosciences ,Aging ,Brain Cancer ,Cancer ,Clinical Research ,Rare Diseases ,Genetics ,Brain Disorders ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Adult ,Age Factors ,Aged ,Biomarkers ,Tumor ,Brain Neoplasms ,Case-Control Studies ,DNA Helicases ,Female ,Follow-Up Studies ,Genetic Predisposition to Disease ,Genotype ,Glioma ,Humans ,Male ,Middle Aged ,Neoplasm Grading ,Polymorphism ,Single Nucleotide ,Prognosis ,Risk Factors ,Telomerase ,age at diagnosis ,glioma ,single nucleotide polymorphism ,telomerase ,telomere ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundGenome-wide association studies have implicated single nucleotide polymorphisms (SNPs) in 7 genes as glioma risk factors, including 2 (TERT, RTEL1) involved in telomerase structure/function. We examined associations of these 7 established glioma risk loci with age at diagnosis among patients with glioma.MethodsSNP genotype data were available for 2286 Caucasian glioma patients from the University of California, San Francisco (n = 1434) and the Mayo Clinic (n = 852). Regression analyses were performed to test for associations between "number of risk alleles" and "age at diagnosis," adjusted for sex and study site and stratified by tumor grade/histology where appropriate.ResultsFour SNPs were significantly associated with age at diagnosis. Carrying a greater number of risk alleles at rs55705857 (CCDC26) and at rs498872 (PHLDB1) was associated with younger age at diagnosis (P = 1.4 × 10(-22) and P = 9.5 × 10(-7), respectively). These SNPs are stronger risk factors for oligodendroglial tumors, which tend to occur in younger patients, and their association with age at diagnosis varied across tumor subtypes. In contrast, carrying more risk alleles at rs2736100 (TERT) and at rs6010620 (RTEL1) was associated with older age at diagnosis (P = 6.2 × 10(-4) and P = 2.5 × 10(-4), respectively). These SNPs are risk factors for all glioma grades/histologies, and their association with age at diagnosis was consistent across tumor subgroups.ConclusionsCarrying a greater number of risk alleles might be expected to decrease age at diagnosis. However, glioma susceptibility conferred by variation in telomerase-related genes did not follow this pattern. This supports the hypothesis that telomerase-related mechanisms of telomere maintenance are more associated with gliomas that develop later in life than those utilizing telomerase-independent mechanisms (ie, alternative lengthening of telomeres).
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- 2013
16. Inherited variant on chromosome 11q23 increases susceptibility to IDH-mutated but not IDH-normal gliomas regardless of grade or histology
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Rice, Terri, Zheng, Shichun, Decker, Paul A, Walsh, Kyle M, Bracci, Paige, Xiao, Yuanyuan, McCoy, Lucie S, Smirnov, Ivan, Patoka, Joseph S, Hansen, Helen M, Hsuang, George, Wiemels, Joe L, Tihan, Tarik, Pico, Alexander R, Prados, Michael D, Chang, Susan M, Berger, Mitchel S, Caron, Alissa, Fink, Stephanie, Kollmeyer, Thomas, Rynearson, Amanda, Voss, Jesse, Kosel, Matthew L, Fridley, Brooke L, Lachance, Daniel H, Eckel-Passow, Jeanette E, Sicotte, Hugues, O'Neill, Brian Patrick, Giannini, Caterina, Wiencke, John K, Jenkins, Robert B, and Wrensch, Margaret R
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Brain Cancer ,Neurosciences ,Cancer ,Brain Disorders ,Clinical Research ,Genetics ,Rare Diseases ,Aetiology ,2.1 Biological and endogenous factors ,Adult ,Biomarkers ,Tumor ,Brain Neoplasms ,Case-Control Studies ,Chromosomes ,Human ,Pair 11 ,Chromosomes ,Human ,Pair 8 ,Female ,Genetic Predisposition to Disease ,Glioma ,Humans ,Isocitrate Dehydrogenase ,Male ,Middle Aged ,Mutation ,Neoplasm Grading ,Neoplasm Staging ,Polymorphism ,Single Nucleotide ,Prognosis ,adult glioma ,IDH1 and IDH2 mutation ,rs498872 ,rs55705857 ,single-nucleotide polymorphism ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
IntroductionRecent 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.MethodsWe 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.ResultsThe 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.ConclusionA variant at the 11q23 locus increases risk for IDH-mutated but not IDH-wild-type gliomas, regardless of grade or histology.
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- 2013
17. Analysis of 60 Reported Glioma Risk SNPs Replicates Published GWAS Findings but Fails to Replicate Associations From Published Candidate‐Gene Studies
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Walsh, Kyle M, Anderson, Erik, Hansen, Helen M, Decker, Paul A, Kosel, Matt L, Kollmeyer, Thomas, Rice, Terri, Zheng, Shichun, Xiao, Yuanyuan, Chang, Jeffrey S, McCoy, Lucie S, Bracci, Paige M, Wiemels, Joe L, Pico, Alexander R, Smirnov, Ivan, Lachance, Daniel H, Sicotte, Hugues, Eckel‐Passow, Jeanette E, Wiencke, John K, Jenkins, Robert B, and Wrensch, Margaret R
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Rare Diseases ,Brain Disorders ,Human Genome ,Prevention ,Brain Cancer ,Neurosciences ,Cancer ,Aetiology ,2.1 Biological and endogenous factors ,Aged ,California ,Case-Control Studies ,Central Nervous System Neoplasms ,DNA Helicases ,ErbB Receptors ,Female ,Genes ,p16 ,Genes ,p53 ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Glioma ,Humans ,Intracellular Signaling Peptides and Proteins ,Male ,Middle Aged ,Nerve Tissue Proteins ,Polymorphism ,Single Nucleotide ,RNA ,Long Noncoding ,Telomerase ,White People ,glioma ,SNP ,GWAS ,candidate-gene ,Public Health and Health Services - Abstract
Genomewide association studies (GWAS) and candidate-gene studies have implicated single-nucleotide polymorphisms (SNPs) in at least 45 different genes as putative glioma risk factors. Attempts to validate these associations have yielded variable results and few genetic risk factors have been consistently replicated. We conducted a case-control study of Caucasian glioma cases and controls from the University of California San Francisco (810 cases, 512 controls) and the Mayo Clinic (852 cases, 789 controls) in an attempt to replicate previously reported genetic risk factors for glioma. Sixty SNPs selected from the literature (eight from GWAS and 52 from candidate-gene studies) were successfully genotyped on an Illumina custom genotyping panel. Eight SNPs in/near seven different genes (TERT, EGFR, CCDC26, CDKN2A, PHLDB1, RTEL1, TP53) were significantly associated with glioma risk in the combined dataset (P < 0.05), with all associations in the same direction as in previous reports. Several SNP associations showed considerable differences across histologic subtype. All eight successfully replicated associations were first identified by GWAS, although none of the putative risk SNPs from candidate-gene studies was associated in the full case-control sample (all P values > 0.05). Although several confirmed associations are located near genes long known to be involved in gliomagenesis (e.g., EGFR, CDKN2A, TP53), these associations were first discovered by the GWAS approach and are in noncoding regions. These results highlight that the deficiencies of the candidate-gene approach lay in selecting both appropriate genes and relevant SNPs within these genes.
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- 2013
18. Genome-wide association study of glioma and meta-analysis
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Rajaraman, Preetha, Melin, Beatrice S, Wang, Zhaoming, McKean-Cowdin, Roberta, Michaud, Dominique S, Wang, Sophia S, Bondy, Melissa, Houlston, Richard, Jenkins, Robert B, Wrensch, Margaret, Yeager, Meredith, Ahlbom, Anders, Albanes, Demetrius, Andersson, Ulrika, Freeman, Laura E Beane, Buring, Julie E, Butler, Mary Ann, Braganza, Melissa, Carreon, Tania, Feychting, Maria, Fleming, Sarah J, Gapstur, Susan M, Gaziano, J Michael, Giles, Graham G, Hallmans, Goran, Henriksson, Roger, Hoffman-Bolton, Judith, Inskip, Peter D, Johansen, Christoffer, Kitahara, Cari M, Lathrop, Mark, Liu, Chenwei, Le Marchand, Loic, Linet, Martha S, Lonn, Stefan, Peters, Ulrike, Purdue, Mark P, Rothman, Nathaniel, Ruder, Avima M, Sanson, Marc, Sesso, Howard D, Severi, Gianluca, Shu, Xiao-Ou, Simon, Matthias, Stampfer, Meir, Stevens, Victoria L, Visvanathan, Kala, White, Emily, Wolk, Alicja, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Decker, Paul, Enciso-Mora, Victor, Fridley, Brooke, Gao, Yu-Tang, Kosel, Matthew, Lachance, Daniel H, Lau, Ching, Rice, Terri, Swerdlow, Anthony, Wiemels, Joseph L, Wiencke, John K, Shete, Sanjay, Xiang, Yong-Bing, Xiao, Yuanyuan, Hoover, Robert N, Fraumeni, Joseph F, Chatterjee, Nilanjan, Hartge, Patricia, and Chanock, Stephen J
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Clinical Research ,Brain Disorders ,Prevention ,Brain Cancer ,Neurosciences ,Cancer ,Human Genome ,Rare Diseases ,Aetiology ,2.1 Biological and endogenous factors ,Aged ,Brain Neoplasms ,Case-Control Studies ,Cohort Studies ,Cyclin-Dependent Kinase Inhibitor p15 ,DNA Helicases ,Female ,Genome-Wide Association Study ,Glioblastoma ,Glioma ,Humans ,Male ,Middle Aged ,Polymorphism ,Single Nucleotide ,Telomerase ,Complementary and Alternative Medicine ,Paediatrics and Reproductive Medicine ,Genetics & Heredity ,Reproductive medicine - Abstract
Gliomas account for approximately 80 % of all primary malignant brain tumors and, despite improvements in clinical care over the last 20 years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case-control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.
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- 2012
19. A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation
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Jenkins, Robert B, Xiao, Yuanyuan, Sicotte, Hugues, Decker, Paul A, Kollmeyer, Thomas M, Hansen, Helen M, Kosel, Matthew L, Zheng, Shichun, Walsh, Kyle M, Rice, Terri, Bracci, Paige, McCoy, Lucie S, Smirnov, Ivan, Patoka, Joseph S, Hsuang, George, Wiemels, Joe L, Tihan, Tarik, Pico, Alexander R, Prados, Michael D, Chang, Susan M, Berger, Mitchel S, Caron, Alissa A, Fink, Stephanie R, Halder, Chandralekha, Rynearson, Amanda L, Fridley, Brooke L, Buckner, Jan C, O'Neill, Brian P, Giannini, Caterina, Lachance, Daniel H, Wiencke, John K, Eckel-Passow, Jeanette E, and Wrensch, Margaret R
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Agricultural ,Veterinary and Food Sciences ,Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,Agricultural Biotechnology ,Cancer ,Rare Diseases ,Brain Cancer ,Brain Disorders ,Neurosciences ,Adult ,Aged ,Astrocytoma ,Case-Control Studies ,Chromosomes ,Human ,Pair 8 ,Female ,Gene Frequency ,Genetic Association Studies ,Genetic Predisposition to Disease ,High-Throughput Nucleotide Sequencing ,Humans ,Intracellular Signaling Peptides and Proteins ,Isocitrate Dehydrogenase ,Male ,Middle Aged ,Oligodendroglioma ,Polymorphism ,Single Nucleotide ,RNA ,Long Noncoding ,Risk Factors ,Sequence Analysis ,DNA ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Variants at 8q24.21 have been shown to be associated with glioma development. By means of tag SNP genotyping and imputation, pooled next-generation sequencing using long-range PCR and subsequent validation SNP genotyping, we identified seven low-frequency SNPs at 8q24.21 that were strongly associated with glioma risk (P=1×10(-25) to 1×10(-14)). The most strongly associated SNP, rs55705857, remained highly significant after individual adjustment for the other top six SNPs and two previously published SNPs. After stratifying by histological and tumor genetic subtype, the most significant associations of rs55705857 were with oligodendroglial tumors and gliomas with mutant IDH1 or IDH2 (odds ratio (OR)=5.1, P=1.1×10(-31) and OR=4.8, P=6.6×10(-22), respectively). Strong associations were observed for astrocytomas with mutated IDH1 or IDH2 (grades 2-4) (OR=5.16-6.66, P=4.7×10(-12) to 2.2×10(-8)) but not for astrocytomas with wild-type IDH1 and IDH2 (smallest P=0.26). The conserved sequence block that includes rs55705857 is consistently modeled as a microRNA.
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- 2012
20. SSBP2 Variants Are Associated with Survival in Glioblastoma Patients
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Xiao, Yuanyuan, Decker, Paul A, Rice, Terri, McCoy, Lucie S, Smirnov, Ivan, Patoka, Joseph S, Hansen, Helen M, Wiemels, Joe L, Tihan, Tarik, Prados, Michael D, Chang, Susan M, Berger, Mitchel S, Kosel, Matthew L, Fridley, Brooke L, Lachance, Daniel H, O'Neill, Brian Patrick, Buckner, Jan C, Thompson, Reid C, Nabors, Louis Burt, Olson, Jeffrey J, Brem, Steve, Madden, Melissa H, Browning, James E, Wiencke, John K, Egan, Kathleen M, Jenkins, Robert B, and Wrensch, Margaret R
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Brain Cancer ,Neurosciences ,Cancer ,Human Genome ,Brain Disorders ,Clinical Research ,Genetics ,Rare Diseases ,Brain Neoplasms ,DNA-Binding Proteins ,Dacarbazine ,Female ,Genome-Wide Association Study ,Glioblastoma ,Humans ,Male ,Middle Aged ,Polymorphism ,Single Nucleotide ,Prognosis ,Temozolomide ,Oncology & Carcinogenesis ,Clinical sciences ,Oncology and carcinogenesis - Abstract
PurposeGlioblastoma is a devastating, incurable disease with few known prognostic factors. Here, we present the first genome-wide survival and validation study for glioblastoma.Experimental designCox regressions for survival with 314,635 inherited autosomal single-nucleotide polymorphisms (SNP) among 315 San Francisco Adult Glioma Study patients for discovery and three independent validation data sets [87 Mayo Clinic, 232 glioma patients recruited from several medical centers in Southeastern United States (GliomaSE), and 115 The Cancer Genome Atlas patients] were used to identify SNPs associated with overall survival for Caucasian glioblastoma patients treated with the current standard of care, resection, radiation, and temozolomide (total n = 749). Tumor expression of the gene that contained the identified prognostic SNP was examined in three separate data sets (total n = 619). Genotype imputation was used to estimate hazard ratios (HR) for SNPs that had not been directly genotyped.ResultsFrom the discovery and validation analyses, we identified a variant in single-stranded DNA-binding protein 2 (SSBP2) on 5q14.1 associated with overall survival in combined analyses (HR, 1.64; P = 1.3 × 10(-6)). Expression of SSBP2 in tumors from three independent data sets also was significantly related to patient survival (P = 5.3 × 10(-4)). Using genotype imputation, the SSBP2 SNP rs17296479 had the strongest statistically significant genome-wide association with poorer overall patient survival (HR, 1.79; 95% CI, 1.45-2.22; P = 1.0 × 10(-7)).ConclusionThe minor allele of SSBP2 SNP rs17296479 and the increased tumor expression of SSBP2 were statistically significantly associated with poorer overall survival among glioblastoma patients. With further confirmation, previously unrecognized inherited variations influencing survival may warrant inclusion in clinical trials to improve randomization. Unaccounted for genetic influence on survival could produce unwanted bias in such studies.
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- 2012
21. Genomic markers of recurrence risk in atypical meningioma following gross total resection
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Vaubel, Rachael A, primary, Kumar, Rahul, additional, Weiskittel, Taylor M, additional, Jenkins, Sarah, additional, Dasari, Surendra, additional, Uhm, Joon H, additional, Lachance, Daniel H, additional, Brown, Paul D, additional, Van Gompel, Jamie J, additional, Jenkins, Robert B, additional, Kipp, Benjamin R, additional, Sukov, William R, additional, Giannini, Caterina, additional, Johnson, Derek R, additional, and Raghunathan, Aditya, additional
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- 2023
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22. Residual Deep Convolutional Neural Network Predicts MGMT Methylation Status
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Korfiatis, Panagiotis, Kline, Timothy L., Lachance, Daniel H., Parney, Ian F., Buckner, Jan C., and Erickson, Bradley J.
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- 2017
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23. Inherited genetics of adult diffuse glioma and polygenic risk scores - a review
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Eckel-Passow, Jeanette E, primary, Lachance, Daniel H, additional, Decker, Paul A, additional, Kollmeyer, Thomas M, additional, Kosel, Matthew L, additional, Drucker, Kristen L, additional, Slager, Susan, additional, Wrensch, Margaret, additional, Tobin, W Oliver, additional, and Jenkins, Robert B, additional
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- 2022
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24. Glioma: interaction of acquired and germline genetics
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Eckel-Passow, Jeanette E., primary, Lachance, Daniel H., additional, and Jenkins, Robert B., additional
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- 2021
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25. Pleomorphic Xanthoastrocytoma: Natural History and Long-Term Follow-Up
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Ida, Cristiane M., Rodriguez, Fausto J., Burger, Peter C., Caron, Alissa A., Jenkins, Sarah M., Spears, Grant M., Aranguren, Dawn L., Lachance, Daniel H., and Giannini, Caterina
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- 2015
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26. Generative Adversarial Networks to Synthesize Missing T1 and FLAIR MRI Sequences for Use in a Multisequence Brain Tumor Segmentation Model
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Conte, Gian Marco, primary, Weston, Alexander D., additional, Vogelsang, David C., additional, Philbrick, Kenneth A., additional, Cai, Jason C., additional, Barbera, Maurizio, additional, Sanvito, Francesco, additional, Lachance, Daniel H., additional, Jenkins, Robert B., additional, Tobin, W. Oliver, additional, Eckel-Passow, Jeanette E., additional, and Erickson, Bradley J., additional
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- 2021
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27. Abstract PO-023: Differentiation of tumefactive multiple sclerosis and glioblastoma using radiomics features extracted from magnetic resonance imaging and machine learning
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Conte, Gian Marco, primary, Eckel-Passow, Jeanette E., additional, Tobin, W. Oliver, additional, Decker, Paul, additional, Lachance, Daniel H., additional, Jenkins, Robert B., additional, and Erickson, Bradley J., additional
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- 2021
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28. Glioma risk associated with extent of estimated European genetic ancestry in African Americans and Hispanics
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Ostrom, Quinn T., Egan, Kathleen M., Nabors, L. Burt, Gerke, Travis, Thompson, Reid C., Olson, Jeffrey J., LaRocca, Renato, Chowdhary, Sajeel, Eckel-Passow, Jeanette E., Armstrong, Georgina, Wiencke, John K., Bernstein, Jonine L., Claus, Elizabeth B., Il'yasova, Dora, Johansen, Christoffer, Lachance, Daniel H., Lai, Rose K., Merrell, Ryan T., Olson, Sara H., Sadetzki, Siegal, Schildkraut, Joellen M., Shete, Sanjay, Houlston, Richard S., Jenkins, Robert B., Wrensch, Margaret R., Melin, Beatrice S., Amos, Christopher I., Huse, Jason T., Barnholtz-Sloan, Jill S., Bondy, Melissa L., Ostrom, Quinn T., Egan, Kathleen M., Nabors, L. Burt, Gerke, Travis, Thompson, Reid C., Olson, Jeffrey J., LaRocca, Renato, Chowdhary, Sajeel, Eckel-Passow, Jeanette E., Armstrong, Georgina, Wiencke, John K., Bernstein, Jonine L., Claus, Elizabeth B., Il'yasova, Dora, Johansen, Christoffer, Lachance, Daniel H., Lai, Rose K., Merrell, Ryan T., Olson, Sara H., Sadetzki, Siegal, Schildkraut, Joellen M., Shete, Sanjay, Houlston, Richard S., Jenkins, Robert B., Wrensch, Margaret R., Melin, Beatrice S., Amos, Christopher I., Huse, Jason T., Barnholtz-Sloan, Jill S., and Bondy, Melissa L.
- Abstract
Glioma incidence is highest in non-Hispanic Whites, and to date, glioma genome-wide association studies (GWAS) to date have only included European ancestry (EA) populations. African Americans and Hispanics in the US have varying proportions of EA, African (AA) and Native American ancestries (NAA). It is unknown if identified GWAS loci or increased EA is associated with increased glioma risk. We assessed whether EA was associated with glioma in African Americans and Hispanics. Data were obtained for 832 cases and 675 controls from the Glioma International Case-Control Study and GliomaSE Case-Control Study previously estimated to have <80% EA, or self-identify as non-White. We estimated global and local ancestry using fastStructure and RFMix, respectively, using 1,000 genomes project reference populations. Within groups with >= 40% AA (AFR(>= 0.4)), and >= 15% NAA (AMR(>= 0.15)), genome-wide association between local EA and glioma was evaluated using logistic regression conditioned on global EA for all gliomas. We identified two regions (7q21.11, p = 6.36 x 10(-4); 11p11.12, p = 7.0 x 10-4) associated with increased EA, and one associated with decreased EA (20p12.13, p = 0.0026) in AFR(>= 0.4). In addition, we identified a peak at rs1620291 (p = 4.36 x 10(-6)) in 7q21.3. Among AMR(>= 0.15), we found an association between increased EA in one region (12q24.21, p = 8.38 x 10(-4)), and decreased EA in two regions (8q24.21, p = 0. 0010; 20q13.33, p = 6.36 x 10(-4)). No other significant associations were identified. This analysis identified an association between glioma and two regions previously identified in EA populations (8q24.21, 20q13.33) and four novel regions (7q21.11, 11p11.12, 12q24.21 and 20p12.13). The identifications of novel association with EA suggest regions to target for future genetic association studies. What's new? Glioma is rare in non-White populations, and most glioma genome-wide association studies have included only primarily
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- 2020
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29. Associations of High-Grade Glioma With Glioma Risk Alleles and Histories of Allergy and Smoking
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Lachance, Daniel H., Yang, Ping, Johnson, Derek R., Decker, Paul A., Kollmeyer, Thomas M., McCoy, Lucie S., Rice, Terri, Xiao, Yuanyuan, Ali-Osman, Francis, Wang, Frances, Stoddard, Shawn M., Sprau, Debra J., Kosel, Matthew L., Wiencke, John K., Wiemels, Joseph L., Patoka, Joseph S., Davis, Faith, McCarthy, Bridget, Rynearson, Amanda L., Worra, Joel B., Fridley, Brooke L., O’Neill, Brian Patrick, Buckner, Jan C., Il’yasova, Dora, Jenkins, Robert B., and Wrensch, Margaret R.
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- 2011
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30. Abstract 1193: Adult diffuse glioma GWAS by molecular subtype identifies variants in D2HGDH, FAM20C and GMEB2
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Eckel-Passow, Jeanette E., primary, Drucker, Kristen L., additional, Kollmeyer, Thomas M., additional, Kosel, Matthew L., additional, Decker, Paul A., additional, Molinaro, Annette M., additional, Rice, Terri, additional, Praska, Corrine E., additional, Clark, Lauren E., additional, Caron, Alissa A., additional, Abyzov, Alexej, additional, Batzler, Anthony, additional, Song, Jun S., additional, Pekmezci, Melike, additional, Hansen, Helen M., additional, McCoy, Lucie S., additional, Bracci, Paige M., additional, Wiemels, Joseph, additional, Wiencke, John K., additional, Francis, Stephen, additional, Burns, Terence C., additional, Giannini, Caterina, additional, Lachance, Daniel H., additional, Wrensch, Margaret, additional, and Jenkins, Robert B., additional
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- 2020
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31. Genomic and Phenotypic Characterization of a Broad Panel of Patient-Derived Xenografts Reflects the Diversity of Glioblastoma
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Vaubel, Rachael A., primary, Tian, Shulan, additional, Remonde, Dioval, additional, Schroeder, Mark A., additional, Mladek, Ann C., additional, Kitange, Gaspar J., additional, Caron, Alissa, additional, Kollmeyer, Thomas M., additional, Grove, Rebecca, additional, Peng, Sen, additional, Carlson, Brett L., additional, Ma, Daniel J., additional, Sarkar, Gobinda, additional, Evers, Lisa, additional, Decker, Paul A., additional, Yan, Huihuang, additional, Dhruv, Harshil D., additional, Berens, Michael E., additional, Wang, Qianghu, additional, Marin, Bianca M., additional, Klee, Eric W., additional, Califano, Andrea, additional, LaChance, Daniel H., additional, Eckel-Passow, Jeanette E., additional, Verhaak, Roel G., additional, Sulman, Erik P., additional, Burns, Terry C., additional, Meyer, Fredrick B., additional, O'Neill, Brian P., additional, Tran, Nhan L., additional, Giannini, Caterina, additional, Jenkins, Robert B., additional, Parney, Ian F., additional, and Sarkaria, Jann N., additional
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- 2020
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32. Frequency of false-positive FISH 1p/19q codeletion in adult diffuse astrocytic gliomas
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Ball, Matthew K, primary, Kollmeyer, Thomas M, additional, Praska, Corinne E, additional, McKenna, Michelle L, additional, Giannini, Caterina, additional, Raghunathan, Aditya, additional, Jentoft, Mark E, additional, Lachance, Daniel H, additional, Kipp, Benjamin R, additional, Jenkins, Robert B, additional, and Ida, Cristiane M, additional
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- 2020
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33. Long-term incidence of glioma in Olmsted County, Minnesota, and disparities in postglioma survival rate: a population-based study
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Ryan, Conor S, primary, Juhn, Young J, primary, Kaur, Harsheen, primary, Wi, Chung-Il, primary, Ryu, Euijung, primary, King, Katherine S, primary, and Lachance, Daniel H, primary
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- 2019
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34. Sex-specific gene and pathway modeling of inherited glioma risk
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Ostrom, Quinn T., Coleman, Warren, Huang, William, Rubin, Joshua B., Lathia, Justin D., Berens, Michael E., Speyer, Gil, Liao, Peter, Wrensch, Margaret R., Eckel-Passow, Jeanette E., Armstrong, Georgina, Rice, Terri, Wiencke, John K., McCoy, Lucie S., Hansen, Helen M., Amos, Christopher I., Bernstein, Jonine L., Claus, Elizabeth B., Houlston, Richard S., Il'yasova, Dora, Jenkins, Robert B., Johansen, Christoffer, Lachance, Daniel H., Lai, Rose K., Merrell, Ryan T., Olson, Sara H., Sadetzki, Siegal, Schildkraut, Joellen M., Shete, Sanjay, Andersson, Ulrika, Rajaraman, Preetha, Chanock, Stephen J., Linet, Martha S., Wang, Zhaoming, Yeager, Meredith, Melin, Beatrice S., Bondy, Melissa L., Barnholtz-Sloan, Jill S., Ostrom, Quinn T., Coleman, Warren, Huang, William, Rubin, Joshua B., Lathia, Justin D., Berens, Michael E., Speyer, Gil, Liao, Peter, Wrensch, Margaret R., Eckel-Passow, Jeanette E., Armstrong, Georgina, Rice, Terri, Wiencke, John K., McCoy, Lucie S., Hansen, Helen M., Amos, Christopher I., Bernstein, Jonine L., Claus, Elizabeth B., Houlston, Richard S., Il'yasova, Dora, Jenkins, Robert B., Johansen, Christoffer, Lachance, Daniel H., Lai, Rose K., Merrell, Ryan T., Olson, Sara H., Sadetzki, Siegal, Schildkraut, Joellen M., Shete, Sanjay, Andersson, Ulrika, Rajaraman, Preetha, Chanock, Stephen J., Linet, Martha S., Wang, Zhaoming, Yeager, Meredith, Melin, Beatrice S., Bondy, Melissa L., and Barnholtz-Sloan, Jill S.
- Abstract
Background To date, genome-wide association studies (GWAS) have identified 25 risk variants for glioma, explaining 30% of heritable risk. Most histologies occur with significantly higher incidence in males, and this difference is not explained by currently known risk factors. A previous GWAS identified sex-specific glioma risk variants, and this analysis aims to further elucidate risk variation by sex using gene- and pathway-based approaches. Methods Results from the Glioma International Case-Control Study were used as a testing set, and results from 3 GWAS were combined via meta-analysis and used as a validation set. Using summary statistics for nominally significant autosomal SNPs (P < 0.01 in a previous meta-analysis) and nominally significant X-chromosome SNPs (P < 0.01), 3 algorithms (Pascal, BimBam, and GATES) were used to generate gene scores, and Pascal was used to generate pathway scores. Results were considered statistically significant in the discovery set when P < 3.3 x 10(-6) and in the validation set when P < 0.001 in 2 of 3 algorithms. Results Twenty-five genes within 5 regions and 19 genes within 6 regions reached statistical significance in at least 2 of 3 algorithms in males and females, respectively. EGFR was significantly associated with all glioma and glioblastoma in males only and a female-specific association in TERT, all of which remained nominally significant after conditioning on known risk loci. There were nominal associations with the BioCarta telomeres pathway in both males and females. Conclusions These results provide additional evidence that there may be differences by sex in genetic risk for glioma. Additional analyses may further elucidate the biological processes through which this risk is conferred.
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- 2019
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35. Aspirin, NSAIDs, and Glioma Risk : Original Data from the Glioma International Case-Control Study and a Meta-analysis
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Amirian, E. Susan, Ostrom, Quinn T., Armstrong, Georgina N., Lai, Rose K., Gu, Xiangjun, Jacobs, Daniel I., Jalali, Ali, Claus, Elizabeth B., Barnholtz-Sloan, Jill S., Il'yasova, Dora, Schildkraut, Joellen M., Ali-Osman, Francis, Sadetzki, Siegal, Jenkins, Robert B., Lachance, Daniel H., Olson, Sara H., Bernstein, Jonine L., Merrell, Ryan T., Wrensch, Margaret R., Johansen, Christoffer, Houlston, Richard S., Scheurer, Michael E., Shete, Sanjay, Amos, Christopher I., Melin, Beatrice S., Bondy, Melissa L., Amirian, E. Susan, Ostrom, Quinn T., Armstrong, Georgina N., Lai, Rose K., Gu, Xiangjun, Jacobs, Daniel I., Jalali, Ali, Claus, Elizabeth B., Barnholtz-Sloan, Jill S., Il'yasova, Dora, Schildkraut, Joellen M., Ali-Osman, Francis, Sadetzki, Siegal, Jenkins, Robert B., Lachance, Daniel H., Olson, Sara H., Bernstein, Jonine L., Merrell, Ryan T., Wrensch, Margaret R., Johansen, Christoffer, Houlston, Richard S., Scheurer, Michael E., Shete, Sanjay, Amos, Christopher I., Melin, Beatrice S., and Bondy, Melissa L.
- Abstract
Background: There have been few studies of sufficient size to address the relationship between glioma risk and the use of aspirin or NSAIDs, and results have been conflicting. The purpose of this study was to examine the associations between glioma and aspirin/NSAID use, and to aggregate these findings with prior published studies using meta-analysis. Methods: The Glioma International Case-Control Study (GICC) consists of 4,533 glioma cases and 4,171 controls recruited from 2010 to 2013. Interviews were conducted using a standardized questionnaire to obtain information on aspirin/NSAID use. We examined history of regular use for ≥6 months and duration-response. Restricted maximum likelihood meta-regression models were used to aggregate site-specific estimates, and to combine GICC estimates with previously published studies. Results: A history of daily aspirin use for ≥6 months was associated with a 38% lower glioma risk, compared with not having a history of daily use [adjusted meta-OR = 0.62; 95% confidence interval (CI), 0.54–0.70]. There was a significant duration-response trend (P = 1.67 × 10−17), with lower ORs for increasing duration of aspirin use. Duration-response trends were not observed for NSAID use. In the meta-analysis aggregating GICC data with five previous studies, there was a marginally significant association between use of aspirin and glioma (mOR = 0.84; 95% CI, 0.70–1.02), but no association for NSAID use. Conclusions: Our study suggests that aspirin may be associated with a reduced risk of glioma. Impact: These results imply that aspirin use may be associated with decreased glioma risk. Further research examining the association between aspirin use and glioma risk is warranted.
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- 2019
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36. Previously identified common glioma risk SNPs are associated with familial glioma
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Ostrom, Quinn T., Armstrong, Georgina, Amos, Christopher I., Bernstein, Jonine L., Claus, Elizabeth B., Eckel-Passow, Jeanette E., Il'yasova, Dora, Johansen, Christoffer, Lachance, Daniel H., Lai, Rose K., Merrell, Ryan T., Olson, Sara H., Schildkraut, Joellen H., Shete, Sanjay S., Houlston, Richard S., Jenkins, Robert B., Wrensch, Margaret R., Melin, Beatrice S., Barnholtz-Sloan, Jill S., Bondy, Melissa L., Ostrom, Quinn T., Armstrong, Georgina, Amos, Christopher I., Bernstein, Jonine L., Claus, Elizabeth B., Eckel-Passow, Jeanette E., Il'yasova, Dora, Johansen, Christoffer, Lachance, Daniel H., Lai, Rose K., Merrell, Ryan T., Olson, Sara H., Schildkraut, Joellen H., Shete, Sanjay S., Houlston, Richard S., Jenkins, Robert B., Wrensch, Margaret R., Melin, Beatrice S., Barnholtz-Sloan, Jill S., and Bondy, Melissa L.
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- 2019
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37. Using germline variants to estimate glioma and subtype risks
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Eckel-Passow, Jeanette E., Decker, Paul A., Kosel, Matt L., Kollmeyer, Thomas M., Molinaro, Annette M., Rice, Terri, Caron, Alissa A., Drucker, Kristen L., Praska, Corinne E., Pekmezci, Melike, Hansen, Helen M., McCoy, Lucie S., Bracci, Paige M., Erickson, Bradley J., Lucchinetti, Claudia F., Wiemels, Joseph L., Wiencke, John K., Bondy, Melissa L., Melin, Beatrice S., Burns, Terry C., Giannini, Caterina, Lachance, Daniel H., Wrensch, Margaret R., Jenkins, Robert B., Eckel-Passow, Jeanette E., Decker, Paul A., Kosel, Matt L., Kollmeyer, Thomas M., Molinaro, Annette M., Rice, Terri, Caron, Alissa A., Drucker, Kristen L., Praska, Corinne E., Pekmezci, Melike, Hansen, Helen M., McCoy, Lucie S., Bracci, Paige M., Erickson, Bradley J., Lucchinetti, Claudia F., Wiemels, Joseph L., Wiencke, John K., Bondy, Melissa L., Melin, Beatrice S., Burns, Terry C., Giannini, Caterina, Lachance, Daniel H., Wrensch, Margaret R., and Jenkins, Robert B.
- 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.
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- 2019
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38. Aspirin, NSAIDs, and glioma risk:Original data from the glioma international case-control study and a meta-analysis
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Susan Amirian, E., Ostrom, Quinn T., Armstrong, Georgina N., Lai, Rose K., Gu, Xiangjun, Jacobs, Daniel I., Jalali, Ali, Claus, Elizabeth B., Barnholtz-Sloan, Jill S., Il'Yasova, Dora, Schildkraut, Joellen M., Ali-Osman, Francis, Sadetzki, Siegal, Jenkins, Robert B., Lachance, Daniel H., Olson, Sara H., Bernstein, Jonine L., Merrell, Ryan T., Wrensch, Margaret R., Johansen, Christoffer, Houlston, Richard S., Scheurer, Michael E., Shete, Sanjay, Amos, Christopher I., Melin, Beatrice, Bondy, Melissa L., Susan Amirian, E., Ostrom, Quinn T., Armstrong, Georgina N., Lai, Rose K., Gu, Xiangjun, Jacobs, Daniel I., Jalali, Ali, Claus, Elizabeth B., Barnholtz-Sloan, Jill S., Il'Yasova, Dora, Schildkraut, Joellen M., Ali-Osman, Francis, Sadetzki, Siegal, Jenkins, Robert B., Lachance, Daniel H., Olson, Sara H., Bernstein, Jonine L., Merrell, Ryan T., Wrensch, Margaret R., Johansen, Christoffer, Houlston, Richard S., Scheurer, Michael E., Shete, Sanjay, Amos, Christopher I., Melin, Beatrice, and Bondy, Melissa L.
- Abstract
Background: There have been few studies of sufficient size to address the relationship between glioma risk and the use of aspirin or NSAIDs, and results have been conflicting. The purpose of this study was to examine the associations between glioma and aspirin/NSAID use, and to aggregate these findings with prior published studies using meta-analysis. Methods: The Glioma International Case-Control Study (GICC) consists of 4,533 glioma cases and 4,171 controls recruited from 2010 to 2013. Interviews were conducted using a standardized questionnaire to obtain information on aspirin/NSAID use. We examined history of regular use for ≥6 months and duration-response. Restricted maximum likelihood meta-regression models were used to aggregate site-specific estimates, and to combine GICC estimates with previously published studies. Results: A history of daily aspirin use for ≥6 months was associated with a 38% lower glioma risk, compared with not having a history of daily use [adjusted meta-OR ¼ 0.62; 95% confidence interval (CI), 0.54-0.70]. There was a significant duration-response trend (P ¼ 1.67 × 10- 17 ), with lower ORs for increasing duration of aspirin use. Duration-response trends were not observed for NSAID use. In the meta-analysis aggregating GICC data with five previous studies, there was a marginally significant association between use of aspirin and glioma (mOR = 0.84; 95% CI, 0.70-1.02), but no association for NSAID use. Conclusions: Our study suggests that aspirin may be associated with a reduced risk of glioma. Impact: These results imply that aspirin use may be associated with decreased glioma risk. Further research examining the association between aspirin use and glioma risk is warranted.
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- 2019
39. Molecular profiling of long-term IDH-wildtype glioblastoma survivors
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Burgenske, Danielle M, primary, Yang, Jie, additional, Decker, Paul A, additional, Kollmeyer, Thomas M, additional, Kosel, Matthew L, additional, Mladek, Ann C, additional, Caron, Alissa A, additional, Vaubel, Rachael A, additional, Gupta, Shiv K, additional, Kitange, Gaspar J, additional, Sicotte, Hugues, additional, Youland, Ryan S, additional, Remonde, Dioval, additional, Voss, Jesse S, additional, Fritcher, Emily G Barr, additional, Kolsky, Kathryn L, additional, Ida, Cristiane M, additional, Meyer, Fredric B, additional, Lachance, Daniel H, additional, Parney, Ian J, additional, Kipp, Benjamin R, additional, Giannini, Caterina, additional, Sulman, Erik P, additional, Jenkins, Robert B, additional, Eckel-Passow, Jeanette E, additional, and Sarkaria, Jann N, additional
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- 2019
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40. Asthma and risk of glioma: a population-based case–control study
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Kaur, Harsheen, primary, Lachance, Daniel H, additional, Ryan, Conor S, additional, Sheen, Youn Ho, additional, Seol, Hee Yun, additional, Wi, Chung-Il, additional, Sohn, Sunghwan, additional, King, Katherine S, additional, Ryu, Euijung, additional, and Juhn, Young, additional
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- 2019
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41. Aspirin, NSAIDs, and Glioma Risk: Original Data from the Glioma International Case–Control Study and a Meta-analysis
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Amirian, E. Susan, primary, Ostrom, Quinn T., additional, Armstrong, Georgina N., additional, Lai, Rose K., additional, Gu, Xiangjun, additional, Jacobs, Daniel I., additional, Jalali, Ali, additional, Claus, Elizabeth B., additional, Barnholtz-Sloan, Jill S., additional, Il'yasova, Dora, additional, Schildkraut, Joellen M., additional, Ali-Osman, Francis, additional, Sadetzki, Siegal, additional, Jenkins, Robert B., additional, Lachance, Daniel H., additional, Olson, Sara H., additional, Bernstein, Jonine L., additional, Merrell, Ryan T., additional, Wrensch, Margaret R., additional, Johansen, Christoffer, additional, Houlston, Richard S., additional, Scheurer, Michael E., additional, Shete, Sanjay, additional, Amos, Christopher I., additional, Melin, Beatrice, additional, and Bondy, Melissa L., additional
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- 2019
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42. Sex-specific genome-wide association study in glioma identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21
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Ostrom, Quinn T., Kinnersley, Ben, Wrensch, Margaret R., Eckel-Passow, Jeanette E., Armstrong, Georgina, Rice, Terri, Chen, Yanwen, Wiencke, John K., McCoy, Lucie S., Hansen, Helen M., Amos, Christopher I., Bernstein, Jonine L., Claus, Elizabeth B., Il’yasova, Dora, Johansen, Christoffer, Lachance, Daniel H., Lai, Rose K., Merrell, Ryan T., Olson, Sara H., Sadetzki, Siegel, Schildkraut, Joellen M., Shete, Sanjay, Rubin, Joshua B., Lathia, Justin D., Berens, Michael E., Andersson, Ulrika, Rajaraman, Preetha, Chanock, Stephen J., Linet, Martha S., Wang, Zhaoming, Yeager, Meredith, Houlston, Richard S., Jenkins, Robert B., Melin, Beatrice, Bondy, Melissa L., and Barnholtz-Sloan, Jill. S.
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Oncology ,0303 health sciences ,medicine.medical_specialty ,Locus (genetics) ,Genome-wide association study ,Single-nucleotide polymorphism ,Biology ,medicine.disease ,Logistic regression ,Sex specific ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Glioma ,Internal medicine ,Epidemiology ,medicine ,030304 developmental biology ,Genetic association - Abstract
Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.
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- 2017
43. Evaluating glioma risk associated with extent of European admixture in African-Americans and Latinos
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Ostrom, Quinn T., Egan, Kathleen M., Nabors, L. Burt, Gerke, Travis, Thompson, Reid C., Olson, Jeffrey J., LaRocca, Renato, Chowdhary, Sajeel, Eckel-Passow, Jeanette E., Armstrong, Georgina, Wiencke, John K., Amos, Christopher I., Bernstein, Jonine L., Claus, Elizabeth B., Il'yasova, Dora, Johansen, Christoffer, Lachance, Daniel H., Lai, Rose, Merrell, Ryan T., Olson, Sara H., Sadetzki, Siegal, Schildkraut, Joellen, Shete, Sanjay, Houlston, Richard S., Jenkins, Robert B., Melin, Beatrice S., Bondy, Melissa L., Barnholtz-Sloan, Jill S., Ostrom, Quinn T., Egan, Kathleen M., Nabors, L. Burt, Gerke, Travis, Thompson, Reid C., Olson, Jeffrey J., LaRocca, Renato, Chowdhary, Sajeel, Eckel-Passow, Jeanette E., Armstrong, Georgina, Wiencke, John K., Amos, Christopher I., Bernstein, Jonine L., Claus, Elizabeth B., Il'yasova, Dora, Johansen, Christoffer, Lachance, Daniel H., Lai, Rose, Merrell, Ryan T., Olson, Sara H., Sadetzki, Siegal, Schildkraut, Joellen, Shete, Sanjay, Houlston, Richard S., Jenkins, Robert B., Melin, Beatrice S., Bondy, Melissa L., and Barnholtz-Sloan, Jill S.
- Abstract
Glioma incidence is highest in non-Hispanic Whites, where it occurs ~2x as frequently compared with other race/ethnicity groups. Glioma GWAS to date have included European ancestry populations only, and it is unknown whether variants identified by these analyses are associated with glioma in non- European ancestry populations. African Americans and Hispanics are admixed populations with varying proportions of European ancestry. While global ancestry may be similar within admixed groups, the proportion of European ancestry at each allele can vary across the genome. As glioma is more common in European ancestry populations, the presence of increased local European ancestry in these admixed populations could be used to identify glioma risk loci. Here we assessed whether excess European ancestry at established risk loci (Melin et al, Nature Genetics, 2017) was associated with glioma risk in non-European ancestry populations. Global ancestry was estimated using fastStructure, and local ancestry was estimated using RFMix. Both methods used 1,000 genomes project reference populations (African: YRI; European: CEU; East Asian: CHB/JPT; and Native American: CLM/PEL/MXL). We evaluated differences in local European ancestry between cases and controls using logistic regression conditioned on global European ancestry within 500kb of 25 previously identified risk variants among individuals with ≥50% African ancestry, and ≥30% Native American ancestry for all gliomas, and for grade IV glioblastoma (GBM) and grade II-III non-GBM. There were 347 individuals (184 cases and 163 controls) with ≥50% global African ancestry, and 277 individuals (153 cases and 124 controls) with ≥30% global American ancestry. There was no significant difference in proportion of global European ancestry between cases and controls with ≥50% global African ancestry (cases: 18.2%, controls: 17.7%, p=0.6834), and no significant difference in proportion of global European ancestry between cases and controls with
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- 2018
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44. Age‐specific genome‐wide association study in glioblastoma identifies increased proportion of 'lower grade glioma'‐like features associated with younger age
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Ostrom, Quinn T., Kinnersley, Ben, Armstrong, Georgina, Rice, Terri, Chen, Yanwen, Wiencke, John K., McCoy, Lucie S., Hansen, Helen M., Amos, Christopher I., Bernstein, Jonine L., Claus, Elizabeth B., Eckel-Passow, Jeanette E., Il'yasova, Dora, Johansen, Christoffer, Lachance, Daniel H., Lai, Rose K., Merrell, Ryan T., Olson, Sara H., Sadetzki, Siegal, Schildkraut, Joellen M., Shete, Sanjay, Rubin, Joshua B., Andersson, Ulrika, Rajaraman, Preetha, Chanock, Stephen J., Linet, Martha S., Wang, Zhaoming, Yeager, Meredith, Houlston, Richard S., Jenkins, Robert B., Wrensch, Margaret R., Melin, Beatrice, Bondy, Melissa L., Barnholtz-Sloan, Jill. S., Ostrom, Quinn T., Kinnersley, Ben, Armstrong, Georgina, Rice, Terri, Chen, Yanwen, Wiencke, John K., McCoy, Lucie S., Hansen, Helen M., Amos, Christopher I., Bernstein, Jonine L., Claus, Elizabeth B., Eckel-Passow, Jeanette E., Il'yasova, Dora, Johansen, Christoffer, Lachance, Daniel H., Lai, Rose K., Merrell, Ryan T., Olson, Sara H., Sadetzki, Siegal, Schildkraut, Joellen M., Shete, Sanjay, Rubin, Joshua B., Andersson, Ulrika, Rajaraman, Preetha, Chanock, Stephen J., Linet, Martha S., Wang, Zhaoming, Yeager, Meredith, Houlston, Richard S., Jenkins, Robert B., Wrensch, Margaret R., Melin, Beatrice, Bondy, Melissa L., and Barnholtz-Sloan, Jill. S.
- Abstract
Glioblastoma (GBM) is the most common malignant brain tumor in the United States. Incidence of GBM increases with age, and younger age‐at‐diagnosis is significantly associated with improved prognosis. While the relationship between candidate GBM risk SNPs and age‐at‐diagnosis has been explored, genome‐wide association studies (GWAS) have not previously been stratified by age. Potential age‐specific genetic effects were assessed in autosomal SNPs for GBM patients using data from four previous GWAS. Using age distribution tertiles (18–53, 54–64, 65+) datasets were analyzed using age‐stratified logistic regression to generate p values, odds ratios (OR), and 95% confidence intervals (95%CI), and then combined using meta‐analysis. There were 4,512 total GBM cases, and 10,582 controls used for analysis. Significant associations were detected at two previously identified SNPs in 7p11.2 (rs723527 [p54–63 = 1.50x10−9, OR54–63 = 1.28, 95%CI54–63 = 1.18–1.39; p64+ = 2.14x10−11, OR64+ = 1.32, 95%CI64+ = 1.21–1.43] and rs11979158 [p54–63 = 6.13x10−8, OR54–63 = 1.35, 95%CI54–63 = 1.21–1.50; p64+ = 2.18x10−10, OR64+ = 1.42, 95%CI64+ = 1.27–1.58]) but only in persons >54. There was also a significant association at the previously identified lower grade glioma (LGG) risk locus at 8q24.21 (rs55705857) in persons ages 18–53 (p18–53 = 9.30 × 10−11, OR18–53 = 1.76, 95%CI18–53 = 1.49–2.10). Within The Cancer Genome Atlas (TCGA) there was higher prevalence of ‘LGG’‐like tumor characteristics in GBM samples in those 18–53, with IDH1/2 mutation frequency of 15%, as compared to 2.1% [54–63] and 0.8% [64+] (p = 0.0005). Age‐specific differences in cancer susceptibility can provide important clues to etiology. The association of a SNP known to confer risk for IDH1/2 mutant glioma and higher prevalence of IDH1/2 mutation within younger individuals 18–53 suggests that more younger individuals may present initially with ‘secondary glioblastoma.’
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- 2018
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45. Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21
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Ostrom, Quinn T., Kinnersley, Ben, Wrensch, Margaret R., Eckel-Passow, Jeanette E., Armstrong, Georgina, Rice, Terri, Chen, Yanwen, Wiencke, John K., McCoy, Lucie S., Hansen, Helen M., Amos, Christopher I., Bernstein, Jonine L., Claus, Elizabeth B., Il'yasova, Dora, Johansen, Christoffer, Lachance, Daniel H., Lai, Rose K., Merrell, Ryan T., Olson, Sara H., Sadetzki, Siegal, Schildkraut, Joellen M., Shete, Sanjay, Rubin, Joshua B., Lathia, Justin D., Berens, Michael E., Andersson, Ulrika, Rajaraman, Preetha, Chanock, Stephen J., Linet, Martha S., Wang, Zhaoming, Yeager, Meredith, Houlston, Richard S., Jenkins, Robert B., Melin, Beatrice S., Bondy, Melissa L., Barnholtz-Sloan, Jill. S., Ostrom, Quinn T., Kinnersley, Ben, Wrensch, Margaret R., Eckel-Passow, Jeanette E., Armstrong, Georgina, Rice, Terri, Chen, Yanwen, Wiencke, John K., McCoy, Lucie S., Hansen, Helen M., Amos, Christopher I., Bernstein, Jonine L., Claus, Elizabeth B., Il'yasova, Dora, Johansen, Christoffer, Lachance, Daniel H., Lai, Rose K., Merrell, Ryan T., Olson, Sara H., Sadetzki, Siegal, Schildkraut, Joellen M., Shete, Sanjay, Rubin, Joshua B., Lathia, Justin D., Berens, Michael E., Andersson, Ulrika, Rajaraman, Preetha, Chanock, Stephen J., Linet, Martha S., Wang, Zhaoming, Yeager, Meredith, Houlston, Richard S., Jenkins, Robert B., Melin, Beatrice S., Bondy, Melissa L., and Barnholtz-Sloan, Jill. S.
- Abstract
Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.
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- 2018
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46. Molecular subtyping of tumors from patients with familial glioma
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Ruiz, Vanessa Y., Praska, Corinne E., Armstrong, Georgina, Kollmeyer, Thomas M., Yamada, Seiji, Decker, Paul A., Kosel, Matthew L., Eckel-Passow, Jeanette E., Lachance, Daniel H., Bainbridge, Matthew N., Melin, Beatrice S., Bondy, Melissa L., Jenkins, Robert B., Ruiz, Vanessa Y., Praska, Corinne E., Armstrong, Georgina, Kollmeyer, Thomas M., Yamada, Seiji, Decker, Paul A., Kosel, Matthew L., Eckel-Passow, Jeanette E., Lachance, Daniel H., Bainbridge, Matthew N., Melin, Beatrice S., Bondy, Melissa L., and Jenkins, Robert B.
- Abstract
Background. Single-gene mutation syndromes account for some familial glioma (FG); however, they make up only a small fraction of glioma families. Gliomas can be classified into 3 major molecular subtypes based on isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion. We hypothesized that the prevalence of molecular subtypes might differ in familial versus sporadic gliomas and that tumors in the same family should have the same molecular subtype. Methods. Participants in the FG study (Gliogene) provided samples for germline DNA analysis. Formalin-fixed, paraffin-embedded tumors were obtained from a subset of FG cases, and DNA was extracted. We analyzed tissue from 75 families, including 10 families containing a second affected family member. Copy number variation data were obtained using a first-generation Affymetrix molecular inversion probe (MIP) array. Results. Samples from 62 of 75 (83%) FG cases could be classified into the 3 subtypes. The prevalence of the molecular subtypes was: 30 (48%) IDH-wildtype, 21 (34%) IDH-mutant non-codeleted, and 11 (19%) IDH-mutant and 1p/19q codeleted. This distribution of molecular subtypes was not statistically different from that of sporadic gliomas (P = 0.54). Of 10 paired FG samples, molecular subtypes were concordant for 7 (kappa = 0.59): 3 IDH-mutant non-codeleted, 2 IDH-wildtype, and 2 IDH-mutant and 1p/19q codeleted gliomas. Conclusions. Our data suggest that within individual families, patients develop gliomas of the same molecular subtype. However, we did not observe differences in the prevalence of the molecular subtypes in FG compared with sporadic gliomas. These observations provide further insight into the distribution of molecular subtypes in FG.
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- 2018
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47. Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer
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Andersson, Ulrika, Wibom, Carl, Cederquist, Kristina, Aradottir, Steina, Borg, Åke, Armstrong, Georgina N., Shete, Sanjay, Lau, Ching C., Bainbridge, Matthew N., Claus, Elizabeth B., Barnholtz-Sloan, Jill, Lai, Rose, Il'yasova, Dora, Houlston, Richard S., Schildkraut, Joellen, Bernstein, Jonine L., Olson, Sara H., Jenkins, Robert B., Lachance, Daniel H., Wrensch, Margaret, Davis, Faith G., Merrell, Ryan, Johansen, Christoffer, Sadetzki, Siegal, Bondy, Melissa L., Melin, Beatrice S., Adatto, Phyllis, Morice, Fabian, Payen, Sam, McQuinn, Lacey, McGaha, Rebecca, Guerra, Sandra, Paith, Leslie, Roth, Katherine, Zeng, Dong, Zhang, Hui, Yung, Alfred, Aldape, Kenneth, Gilbert, Mark, Weinberger, Jeffrey, Colman, Howard, Conrad, Charles, de Groot, John, Forman, Arthur, Groves, Morris, Levin, Victor, Loghin, Monica, Puduvalli, Vinay, Sawaya, Raymond, Heimberger, Amy, Lang, Frederick, Levine, Nicholas, Tolentino, Lori, Saunders, Kate, Thach, Thu-Trang, Iacono, Donna Dello, Sloan, Andrew, Gerson, Stanton, Selman, Warren, Bambakidis, Nicholas, Hart, David, Miller, Jonathan, Hoffer, Alan, Cohen, Mark, Rogers, Lisa, Nock, Charles J, Wolinsky, Yingli, Devine, Karen, Fulop, Jordonna, Barrett, Wendi, Shimmel, Kristen, Ostrom, Quinn, Barnett, Gene, Rosenfeld, Steven, Vogelbaum, Michael, Weil, Robert, Ahluwalia, Manmeet, Peereboom, David, Staugaitis, Susan, Schilero, Cathy, Brewer, Cathy, Smolenski, Kathy, McGraw, Mary, Naska, Theresa, Ram, Zvi, Blumenthal, Deborah T., Bokstein, Felix, Umansky, Felix, Zaaroor, Menashe, Cohen, Avi, Tzuk-Shina, Tzeela, Voldby, Bo, Laursen, René, Andersen, Claus, Brennum, Jannick, Henriksen, Matilde Bille, Marzouk, Maya, Davis, Mary Elizabeth, Boland, Eamon, Smith, Marcel, Eze, Ogechukwu, Way, Mahalia, Lada, Pat, Miedzianowski, Nancy, Frechette, Michelle, Paleologos, Nina, Byström, Gudrun, Svedberg, Eva, Huggert, Sara, Kimdal, Mikael, Sandström, Monica, Brännström, Nikolina, Hayat, Amina, Tihan, Tarik, Zheng, Shichun, Berger, Mitchel, Butowski, Nicholas, Chang, Susan, Clarke, Jennifer, Prados, Michael, Rice, Terri, Sison, Jeannette, Kivett, Valerie, Duo, Xiaoqin, Hansen, Helen, Hsuang, George, Lamela, Rosito, Ramos, Christian, Patoka, Joe, Wagenman, Katherine, Zhou, Mi, Klein, Adam, McGee, Nora, Pfefferle, Jon, Wilson, Callie, Morris, Pagan, Hughes, Mary, Britt-Williams, Marlin, Foft, Jessica, Madsen, Julia, Polony, Csaba, McCarthy, Bridget, Zahora, Candice, Villano, John, Engelhard, Herbert, Borg, Ake, Chanock, Stephen K, Collins, Peter, Elston, Robert, Kleihues, Paul, Kruchko, Carol, Petersen, Gloria, Plon, Sharon, Thompson, Patricia, Johansen, C., Sadetzki, S., Melin, B., Scheurer, Michael E., Liu, Yanhong, Yu, Robert K., Aldape, Kenneth D., Gilbert, Mark R., Weinberg, Jeffrey, Hosking, Fay J., Robertson, Lindsay, Papaemmanuil, Elli, Sloan, Andrew E., McKean-Cowdin, Roberta, Yechezkel, Galit Hirsh, Bruchim, Revital Bar-Sade, Aslanov, Lili, Kosteljanetz, Michael, Broholm, Helle, Schubert, Erica, DeAngelis, Lisa, Yang, Ping, Rynearson, Amanda, Henriksson, Roger, Lada, Patricia, Wiencke, John, Wiemels, Joe, McCoy, Lucie, and McCarthy, Bridget J.
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Male ,Cancer Research ,Neurologi ,Colorectal cancer ,Bioinformatics ,Germline ,0302 clinical medicine ,glioma ,Medicine ,TP53 ,Family history ,Melanoma ,family history ,0303 health sciences ,Brain Neoplasms ,MLH1 ,Nuclear Proteins ,CDKN2A/B ,Middle Aged ,Pedigree ,3. Good health ,MutS Homolog 2 Protein ,Neurology ,Oncology ,Child, Preschool ,030220 oncology & carcinogenesis ,Basic and Translational Investigations ,Colonic Neoplasms ,Female ,MutL Protein Homolog 1 ,Adult ,Breast Neoplasms ,Young Adult ,03 medical and health sciences ,Germline mutation ,Breast cancer ,Glioma ,Humans ,Genetic Predisposition to Disease ,neoplasms ,Cyclin-Dependent Kinase Inhibitor p16 ,Germ-Line Mutation ,Adaptor Proteins, Signal Transducing ,Cyclin-Dependent Kinase Inhibitor p15 ,030304 developmental biology ,Cancer och onkologi ,business.industry ,Cancer ,medicine.disease ,MSH2 ,nervous system diseases ,Checkpoint Kinase 2 ,Cancer and Oncology ,Cancer research ,Neurology (clinical) ,Tumor Suppressor Protein p53 ,business - Abstract
Background: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers. Methods: Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer. The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were selected because these genes have been previously reported to be associated with cancer pedigrees known to include glioma. Results: We detected a single structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one family with 3 cases with glioma and one relative with colon cancer. Conclusions: Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes. Meeting Abstract: P04.02 published in the same journal, Vol. 16, Suppl. 2.
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- 2014
48. Long-term incidence of glioma in Olmsted County, Minnesota, and disparities in postglioma survival rate: a population-based study.
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Ryan, Conor S, Juhn, Young J, Kaur, Harsheen, Wi, Chung-Il, Ryu, Euijung, King, Katherine S, and Lachance, Daniel H
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GLIOMAS ,AMERICANS ,GLIOBLASTOMA multiforme ,OLIGODENDROGLIOMAS - Abstract
Background We assessed glioma incidence and disparities in postglioma survival rate in the Olmsted County, Minnesota, population. Methods This population-based study assessed the incidence of pathologically confirmed primary gliomas between January 1, 1995, and December 31, 2014. Age- and sex-adjusted incidence rates per 100 000 person-years were calculated and standardized to the US white 2010 population. We compared incidence trends of glioma during our study period with previously published Olmsted County data from 1950 to 1990. We assessed postglioma survival rates among individuals with different socioeconomic status (SES), which was measured by a validated individual HOUsing-based SES index (HOUSES). Results We identified 135 incident glioma cases (93% white) with 20 pediatric (50% female) and 115 adult cases (44% female). Overall incidence rate during our study period, 5.51 per 100 000 person-years (95% CI: 4.56-6.46), showed no significant changes and was similar to that seen in 1950 to 1990, 5.5 per 100 000 person-years. The incidence of pediatric (age < 20 years) glioma was 2.49 (95% CI: 1.40-3.58), whereas adult glioma incidence was 6.47 (95% CI: 5.26-7.67). Among those with grade II to IV gliomas, individuals with lower SES (< median HOUSES) had significantly lower 5-year survival rates compared to those with higher SES, adjusted hazard ratio 1.61 (95% CI: 1.01-2.85). Conclusion In a well-defined North American population, long-term glioma incidence appears stable since 1950. Significant socioeconomic disparities exist for postglioma survival. [ABSTRACT FROM AUTHOR]
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- 2020
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49. Preliminary exploration of a computerized cognitive battery and comparison with traditional testing in patients with high-grade glioma
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Cerhan, Jane H, primary, Caine, Chip, additional, Anderson, S Keith, additional, Johnson, Derek R, additional, Lachance, Daniel H, additional, Yan, Elizabeth, additional, and Brown, Paul D, additional
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- 2018
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50. Preliminary exploration of a computerized cognitive battery and comparison with traditional testing in patients with high-grade glioma.
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Cerhan, Jane H, Caine, Chip, Anderson, S Keith, Johnson, Derek R, Lachance, Daniel H, Yan, Elizabeth, and Brown, Paul D
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BRAIN tumors - Abstract
Background Cognitive function is an important outcome measure in many brain tumor clinical trials, and investigators are interested in employing the most efficient methods of cognitive assessment for this purpose. Computerized testing can be appealing because of the perceived ease of use and electronic data generated. Traditional tests may have the advantage of accumulated validity evidence and comparability across historic trials. Methods We evaluated feasibility of a Cogstate battery in 39 patients with high-grade glioma, and compared it with a commonly used paper-and-pencil battery. Results Both batteries were well tolerated and rated equally likeable. Correlations between the batteries were low to low-moderate. More patients showed impairment at baseline and decline across trials on traditional tests. Conclusions Both batteries were well tolerated, but the most complicated tasks (from both batteries) could not be completed by all subjects. Preliminary validity evidence for the Cogstate tasks was mixed, but a larger sample is needed. [ABSTRACT FROM AUTHOR]
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- 2019
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