Evidence map›Paper›PMID 22497777›Full record

ArticleDNA repair2012

Increased risk of lung cancer associated with a functionally impaired polymorphic variant of the human DNA glycosylase NEIL2.

Sanjib Dey, Amit K Maiti, Muralidhar L Hegde, Pavana M Hegde, Istvan Boldogh, Partha S Sarkar, Sherif Z Abdel-Rahman, Altaf H Sarker, Bo Hang, Jingwu Xie and 9 more

Abstract read
In one paragraph

Article in DNA repair, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
1.5field-weighted citation impact, top 19% of its field
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

32 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Research progress on the role of the NEIL family in cancer.Frontiers in cell and developmental biology · 2025
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. A Low-Activity Polymorphic Variant of Human NEIL2 DNA Glycosylase.International journal of molecular sciences · 2022
    Article
  12. Article
  13. DNA glycosylase NEIL2 functions in multiple cellular processes.Progress in biophysics and molecular biology · 2021
    Review
  14. Article
  15. The Journal of biological chemistry · 2020
    Article
  16. Article
  17. Review
  18. Article
  19. DNA Damage in Chronic Kidney Disease: Evaluation of Clinical Biomarkers.Oxidative medicine and cellular longevity · 2016
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 6 institutions in 2 countries.

Sanjib DeyDepartment of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
Amit K Maiti
Muralidhar L Hegde
Pavana M Hegde
Istvan Boldogh
Partha S Sarkar
Sherif Z Abdel-Rahman
Altaf H Sarker
Bo Hang
Jingwu Xie
Alan E Tomkinson
Mian Zhou
Binghui Shen
Guanghai Wang
Chen Wu
Dianke Yu
Dongxin Lin
Victor Cardenas
Tapas K Hazra
The University of Texas Medical Branch at Galveston · USChinese Academy of Medical Sciences & Peking Union Medical College · CNCity of Hope · USLawrence Berkeley National Laboratory · USIndiana University – Purdue University Indianapolis · USUNM Comprehensive Cancer Center

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI Gregory L Hura · 2001 to 2026
$89.6M
Synthetic Organic Chemistry CoreP30ES006676 · NIEHS · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI ELFERINK, CORNELIS JOHAN · 1995 to 2017
$21.7M
Roles of LIG3 and XRCC1 genes in genome stability.R01ES012512 · NIEHS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Alan E Tomkinson · 2004 to 2026
$6.3M
Preferential single-strand break repair in the active genes of mammalian cellsR01NS073976 · NINDS · UNIVERSITY OF TEXAS MED BR GALVESTON · PI HAZRA, TAPAS K · 2012 to 2021
$3.3M
Repair of Oxidized Bases in Mammalian GenomesR01CA081063 · NCI · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI MITRA, SANKAR · 1999 to 2012
$3.1M
Molecular Basis of Hedgehog Signaling in CarcinogenesisR01CA094160 · NCI · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI XIE, JINGWU · 2002 to 2011
$2.8M
Linkage of Lung Inflammation to 8-oxoguanine and OGG1R01ES018948 · NIEHS · UNIVERSITY OF TEXAS MED BR GALVESTON · PI BOLDOGH, ISTVAN STEVEN · 2010 to 2014
$1.5M
Repair of oxidative damage in mammalian genomesR01CA102271 · NCI · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI HAZRA, TAPAS K · 2005 to 2010
$1.4M
Polymorphic variants of human DNA glycosylase NEIL2 and lung cancer susceptibilitR21ES017353 · NIEHS · UNIVERSITY OF TEXAS MED BR GALVESTON · PI HAZRA, TAPAS K · 2009 to 2010
$415k
Lung and other cancer etiological model of BER gene polymorphismsR21CA143583 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI SHEN, BINGHUI · 2010 to 2011
$392k
NCI NIH HHS CA102271NCI NIH HHS CA81063NCI NIH HHS CA92584NCI NIH HHS CA94160NCI NIH HHS P01 CA092584NCI NIH HHS R01 CA081063NCI NIH HHS R01 CA094160NCI NIH HHS R01 CA102271NCI NIH HHS R21 CA143583NCI NIH HHS R21CA143583NIEHS NIH HHS ES012512NIEHS NIH HHS ES017353NIEHS NIH HHS P30 ES006676NIEHS NIH HHS R01 ES012512NIEHS NIH HHS R01 ES018948NIEHS NIH HHS R21 ES017353NINDS NIH HHS R01 NS073976
6 · The paper itself

Abstract

Human NEIL2, one of five oxidized base-specific DNA glycosylases, is unique in preferentially repairing oxidative damage in transcribed genes. Here we show that depletion of NEIL2 causes a 6-7-fold increase in spontaneous mutation frequency in the HPRT gene of the V79 Chinese hamster lung cell line. This prompted us to screen for NEIL2 variants in lung cancer patients' genomic DNA. We identified several polymorphic variants, among which R103Q and R257L were frequently observed in lung cancer patients. We then characterized these variants biochemically, and observed a modest decrease in DNA glycosylase activity relative to the wild type (WT) only with the R257L mutant protein. However, in reconstituted repair assays containing WT NEIL2 or its R257L and R103Q variants together with other DNA base excision repair (BER) proteins (PNKP, Polβ, Lig IIIα and XRCC1) or using NEIL2-FLAG immunocomplexes, an ~5-fold decrease in repair was observed with the R257L variant compared to WT or R103Q NEIL2, apparently due to the R257L mutant's lower affinity for other repair proteins, particularly Polβ. Notably, increased endogenous DNA damage was observed in NEIL2 variant (R257L)-expressing cells relative to WT cells. Taken together, our results suggest that the decreased DNA repair capacity of the R257L variant can induce mutations that lead to lung cancer development.

Indexed as

Polymorphism, Single NucleotideAgedAnimalsBlotting, WesternCell LineCHO CellsCricetinaeCricetulusDNA-(Apurinic or Apyrimidinic Site) LyaseDNA DamageDNA GlycosylasesDNA RepairFemaleGene Expression Regulation, EnzymologicGene FrequencyGenotypeDNA-(Apurinic or Apyrimidinic Site) LyaseDNA GlycosylasesHypoxanthine PhosphoribosyltransferaseNEIL2 protein, humanOligonucleotides, Antisense

Identifiers

PMID22497777
PMCPMC3361577
OpenAlexW1989061393

What OpenQuestion holds

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Registered trials

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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.