Evidence map›Paper›PMID 39745907›Full record

ArticleNeuro-oncology2025

Functional germline variants in DNA damage repair pathways are associated with altered survival in adults with glioma treated with temozolomide.

Geno Guerra, George Wendt, Lucie McCoy, Helen M Hansen, Linda Kachuri, Annette M Molinaro, Terri Rice, Victoria Guan, Lianne Capistrano, Allison Hsieh and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Genomic Impacts of Biological Exposures.Journal of developmental biology · 2026
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Geno GuerraDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0001-9870-9998
George WendtDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Lucie McCoyDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-2728-6083
Helen M HansenDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Linda KachuriStanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-3226-4727
Annette M MolinaroDepartment of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
Terri RiceDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Victoria GuanSchool of Pharmacy, University of California San Francisco, San Francisco, CA, USA.
Lianne CapistranoSchool of Pharmacy, University of California San Francisco, San Francisco, CA, USA.
Allison HsiehSchool of Pharmacy, University of California San Francisco, San Francisco, CA, USA.
Veruna KalsiSchool of Pharmacy, University of California San Francisco, San Francisco, CA, USA.
Jaimie SalleeSchool of Pharmacy, University of California San Francisco, San Francisco, CA, USA.
Jennie W TaylorDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0003-3980-5626
Jennifer L ClarkeDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
Eduardo Rodriguez AlmarazDepartment of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
John K WienckeDepartment of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
Jeanette E Eckel-PassowDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Robert B JenkinsDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-4049-694X
Margaret WrenschDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Stephen S FrancisWeill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-6488-6272

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Lila J. Rutten · 1985 to 2026
$151.3M
UCSF CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR024131 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOHNSTON, S. CLAIBORNE · 2006 to 2011
$111.2M
Tissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2002 to 2026
$57.4M
GENETIC EPIDEMIOLOGY OF MALIGNANT GLIOMAR01CA052689 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WIENCKE, JOHN K., WRENSCH, MARGARET R. · 1991 to 2015
$20.5M
International Case Control Study of Malignant GliomaR01CA139020 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BONDY, MELISSA L. · 2010 to 2015
$16.0M
Discovering Infection-mediated Pathways of Glioma Etiology and Prognosis by Leveraging Multiplex Serology and ImmunogenomicsR01CA266676 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FRANCIS, STEPHEN STARKO · 2022 to 2025
$2.6M
Biomarkers of survival in glioma epidemiologyR01CA126831 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WIENCKE, JOHN K. · 2008 to 2013
$2.5M
Training in the Molecular & Genetic Epidemiology of CancerT32CA112355 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, IONA C, ZIV, ELAD · 2020 to 2024
$1.8M
California Department of Public HealthCenters for Disease Control and Prevention's (CDC) National Program of Cancer Registriesloglio CollectiveMayo ClinicNational Brain Tumor FoundationNational Brain Tumor SocietyNational Cancer Institute's Surveillance, Epidemiology and End Results ProgramNCATS NIH HHSNCI NIH HHS P30 CA015083NCI NIH HHS P50 CA097257NCI NIH HHS R01 CA052689NCI NIH HHS R01 CA126831NCI NIH HHS R01 CA139020NCI NIH HHS R01 CA266676NCI NIH HHS T32 CA112355NCRR NIH HHS UL1 RR024131NIH HHS P50CA097257NIH HHS R01CA126831NIH HHS R01CA139020NIH HHS R01CA266676NIH HHS R01CA52689NIH HHS T32CA112355Robert Magnin Newman Endowed Chair in Neuro-oncologyStanley D. Lewis and Virginia S. Lewis Endowed Chair in Brain Tumor ResearchTing Tsung and Wei Fong Chao Foundation
6 · The paper itself

Abstract

backgroundTemozolomide (TMZ) treatment has demonstrated a variable impact on glioma prognosis. This study examines associations of survival with DNA repair gene germline polymorphisms among glioma patients who did and did not have TMZ treatment. Identifying genetic markers which sensitize tumor cells to TMZ could personalize therapy and improve outcomes.

methodsWe evaluated TMZ-related survival associations of pathogenic germline SNPs and genetically predicted transcript levels within 34 DNA repair genes among 1504 glioma patients from the University of California San Francisco Adult Glioma Study (UCSF AGS) and Mayo Clinic, whose diagnoses spanned pre- and post-TMZ eras within the major known glioma prognostic molecular subtypes.

resultsAmong those who received TMZ, 5 SNPs were associated with overall survival, but not in those who did not receive TMZ. Only rs2308321-G, in MGMT, was associated with decreased survival (hazard ratio = 1.21, P = .019) for all glioma subtypes. Rs73191162-T (near UNG), rs13076508-C (near PARP3), rs7840433-A (near NEIL2), and rs3130618-A (near MSH5) were only associated with survival and TMZ treatment for certain subtypes, suggesting subtype-specific germline chemosensitization. Genetically predicted elevated expression of PNKP, compared to normal brain expression, was associated with markedly poor survival in TMZ-treated patients with isocitrate dehydrogenase (IDH)-mutant and 1p/19q non-codeleted gliomas (P = .015), with a median difference of over 70 months in overall survival times. Similarly, NEIL2 and TDG expressions were associated with altered TMZ-related survival only among certain subtypes.

conclusionsFunctional germline alterations within DNA repair genes were associated with TMZ sensitivity, measured by overall survival among adults with glioma. These variants should be evaluated in prospective analyses and functional studies.

Indexed as

Antineoplastic Agents, AlkylatingBrain NeoplasmsDNA DamageDNA RepairGerm-Line MutationGliomaPolymorphism, Single NucleotideAdultAgedBiomarkers, TumorDNA Repair EnzymesFemaleFollow-Up StudiesHumansMaleMiddle AgedAntineoplastic Agents, AlkylatingBiomarkers, TumorDNA Repair EnzymesTemozolomideDNA damage repairgliomapharmacogenomicssurvivaltemozolomide

Identifiers

PMID39745907
PMCPMC12187373

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.