Genetic variation in the <i>NEIL2</i> DNA glycosylase gene is associated with oxidative DNA damage in <i>BRCA2</i> mutation carriers

Benítez‐Buelga, Carlos; Baquero, Juan Miguel; Vaclová, Tereza; Fernández, Victoria; Martin, P M; Inglada‐Pérez, Lucía; Urioste, Miguel; Osorio, Ana; Benı́tez, Javier

doi:10.18632/oncotarget.22638

Cited by 15 publications

(11 citation statements)

References 33 publications

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“…NEIL2 is involved in DNA repair mechanisms, and research suggest it influences malignancies beyond bladder cancer. Alterations in normal NEIL2 activity most likely result in accumulated oxidative damage, as elegantly presented by Benitez-Buelga et al (19).…”

Section: Discussionmentioning

confidence: 79%

External Replication of Urinary Bladder Cancer Prognostic Polymorphisms in the UK Biobank

et al. 2019

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Introduction: Multiple studies have reported genetic associations with prognostic outcomes of urinary bladder cancer. However, the lack of replication of these associations prohibits establishing further evidence-based research directions. Moreover, there is a lack of independent bladder cancer patient samples that contain prognostic measures, making genetic replication analyses even more challenging.Materials and Methods: We have identified 1,534 eligible patients and used data on Hospital Episode Statistics in the UK Biobank to model variables of otherwise non-collected events on bladder cancer recurrence and progression. Data on survival was extracted from the Death Registry. We have used SNPTEST software to replicate previously reported genetic associations with bladder cancer recurrence (N = 69), progression (N = 23), survival (N = 53), and age at the time of diagnosis (N = 20).Results: Using our algorithm, we have identified 618 recurrence and 58 UBC progression events. In total, there were 209 deaths (106 UBC-specific). In replication analyses, eight SNPs have reached nominal statistical significance (p < 0.05). Rs2042329 (CWC27) for UBC recurrence; rs804256, rs4639, and rs804276 (in/close to NEIL2) for NMIBC recurrence; rs2293347 (EGFR) for UBC OS; rs3756712 (PDCD6) for NMIBC OS; rs2344673 (RGS5) for MIBC OS, and rs2297518 (NOS2) for UBC progression. However, none have remained significant after adjustments for multiple comparisons.Discussion: External replication in genetic epidemiology is an essential step to identify credible findings. In our study, we identify potential genetic targets of higher interest for UBC prognosis. In addition, we propose an algorithm for identifying UBC recurrence and progression using routinely-collected data on patient interventions.

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Section: Discussionmentioning

confidence: 79%

External Replication of Urinary Bladder Cancer Prognostic Polymorphisms in the UK Biobank

et al. 2019

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“…A recent analysis of copy number variation using the data from COSMIC and TCGA databases revealed that NEIL2's level is generally low in most cancers (31,32). We and others have also reported that functional variants of NEIL2 are risk factors for lung cancer, squamous cell carcinoma and breast cancer in BRCA2 mutation carriers (33)(34)(35)(36). Although Neil2-null (Neil2 -/-) mice are viable and do not show spontaneous tumor development (17,37), their susceptibility to inflammatory stimuli prompted us to explore the mechanistic basis of NEIL2's role in innate immunity.…”

Section: Introductionmentioning

confidence: 73%

Intrapulmonary administration of purified NEIL2 abrogates NF-κB–mediated inflammation

Tapryal

Shahabi

Chakraborty

et al. 2021

Journal of Biological Chemistry

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…For some missense variants in OGG1, the risk increases by 14-fold (p < 0.01) and reach 18-fold (p < 0.004) in breast cancer patients compared with controls 57 . Also, some common regulatory variants in OGG1 and other DNA glycosidase like NEIL2 are classi ed as potential cancer risk modi ers for BRCA1 and BRCA2 mutations carriers because they exert a synergetic effect with BRCA mutations on DNA damage and telomere shortening 15,58 .…”

Section: Discussionmentioning

confidence: 99%

Whole exome sequencing reveals a combination of rare high and low penetrance variants that correlates with familial breast cancer relative risk

Rekaya

Hamdi

Benna

et al. 2020

Preprint

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Background: Genetic risk factors of breast cancer are very heterogeneous and complex. They vary according to the familial relative risk, the age of cancer diagnosis of the index case and the age of the affected relatives.Objectives: We aimed to investigate and identify simultaneously all rare pathogenic and common variants in unrelated BC cases with different relative risk ratios for breast cancer and evaluate the contribution of these variants in genetic susceptibility to breast cancer.Patients and Methods: All frequent mutations in BRCA genes previously identified in Tunisia have been excluded by Sanger sequencing in 42 women affected with high family risk having at least 3 cancer affected related individuals. Two unrelated cases having two different family histories (in terms of different numbers of affected first-degree relatives and young age onset) have been selected for whole exome sequencing. The first family is composed of three sisters F1.1, F1.2 and F1.3 affected at 46, 50, and 32 years old, respectively. The second has only two breast cancer cases, F2.2 and F2.4, affected at late age 61 and 70 years old, respectively, in addition to other 5 members affected by different kinds of cancer. Selected high risk variants were confirmed and segregation analysis was performed using Sanger sequencing. Results and discussion: For F1.1 case, we identified a pathogenic frame-shift loss of function variant in BRCA2 p.Val1283Lysfs. For F2.2 we identified a pathogenic rare variant in OGG1, p.Arg46Gln that co-segregates with a rare non sense variant in BRCA2 p.K3326X, only in the breast cancer affected cases. Moreover, F2.2 patient has 9 other common low penetrant variants in different loci known to represent independently minor, but cumulatively significant, increased risk for breast cancer.Conclusion: Family history and the young age at onset for patient F1.1 correlate with the presence of a rare high penetrant variant (p.Val1283Lysfs) in BRCA2 gene. However, the late age at onset and the less severe phenotype for patient F2.2 are probably the consequence of the presence of a pathogenic variant p.Arg46Gln in OGG1 gene that co-segregate with a low penetrant variant Lys3326X in BRCA2 only in breast cancer cases.

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Genetic variation in the NEIL2 DNA glycosylase gene is associated with oxidative DNA damage in BRCA2 mutation carriers

Cited by 15 publications

References 33 publications

External Replication of Urinary Bladder Cancer Prognostic Polymorphisms in the UK Biobank

External Replication of Urinary Bladder Cancer Prognostic Polymorphisms in the UK Biobank

Intrapulmonary administration of purified NEIL2 abrogates NF-κB–mediated inflammation

Whole exome sequencing reveals a combination of rare high and low penetrance variants that correlates with familial breast cancer relative risk

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