Molecular epidemiology of DNA repair gene polymorphisms and head and neck cancer

Background: Accumulated evidence shows that DNA repair gene X-ray repair cross complementing group 1 (XRCC1) may determine individual susceptibility to head and neck cancer (HNC) as a major DNA repair gene. However, the results from previous studies have been conflictive and inconsistent. In order to more accurately estimate and integrate the association between XRCC1 Arg399Gln polymorphism and HNC risk, we conducted a meta-analysis including 14586 subjects. Methods: In this meta-analysis, literatures were collected up until September 15, 2020 through multifarious retrieval strategies by searching through electronic databases of PubMed, Cochrane Library, EMBASE, Medline, Web of Science and CNKI. The association between the XRCC1 Arg399Gln polymorphism and HNC was analyzed through calculating summary odds ratios (OR) and 95% confidence intervals (CI). Results: Thirty-one studies consisting of 6025 cases and 8561 controls were identified and analyzed. No significant association between XRCC1 Arg399Gln polymorphisms and HNC risk was found under the allelic (OR = 0.94, 95% CI: 0.82-1.07, P = 0.35), homozygous (OR = 0.99, 95% CI: 0.81-1.21, P = 0.91), heterozygous (OR = 1.01, 95% CI: 0.90-1.13, P = 0.91), dominant (OR = 1.05, 95% CI: 0.85-1.29, P = 0.67) or recessive (OR = 0.93, 95% CI: 0.80-1.08, P = 0.35) genetic models in the overall comparison. In addition, subgroup analyses according to tumor site also displayed no significant association between XRCC1 Arg399Gln polymorphisms and HNC risk. However, subgroup analyses based on ethnicity indicated that HNC risk was significantly related to Arg399Gln genetic heterozygous model (OR = 1.21, 95%CI: 1.04-1.42, P = 0.02) and dominant model (OR = 1.27, 95%CI: 1.02-1.60, P = 0.04) in Caucasians populations. Conclusion: The results from this meta-analysis suggest that the XRCC1 Arg399Gln variants (Arg/Gln and Arg/Arg+Arg/Gln) may contribute to high HNC risk among Caucasians. Further well-designed studies and larger sample sizes are needed to validate our findings.

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Polymorphisms of the DNA repair gene MGMT and risk and progression of head and neck cancer

DNA Repair ◽

10.1016/j.dnarep.2010.02.006 ◽

2010 ◽

Vol 9 (5) ◽

pp. 558-566 ◽

Cited By ~ 13

Author(s):

Zhengdong Zhang ◽

Luo Wang ◽

Sheng Wei ◽

Zhensheng Liu ◽

Li-E. Wang ◽

...

Keyword(s):

Dna Repair ◽

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Repair Gene ◽

Dna Repair Gene

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Abstract 5546: Impact of DNA repair and apoptosis gene polymorphisms on clinical outcome in head and neck cancer patients treated with radiotherapy

10.1158/1538-7445.am2014-5546 ◽

2014 ◽

Author(s):

Marie-Christine Etienne-Grimaldi ◽

Delphine Borchiellini ◽

Laurence LLorca ◽

Jean-Louis Formento ◽

Patricia Formento ◽

...

Keyword(s):

Dna Repair ◽

Head And Neck Cancer ◽

Clinical Outcome ◽

Head And Neck ◽

Cancer Patients ◽

Neck Cancer ◽

Gene Polymorphisms ◽

Apoptosis Gene

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Dna-Repair Gene Polymorphisms Associated with Favorable Clinical Outcome Following Cetuximab-Based Therapy for Elderly and Multi-Morbid Patients with Primary and Recurrent Squamous Cell Carcinoma of the Head and Neck

Annals of Oncology ◽

10.1016/s0923-7534(20)33610-3 ◽

2012 ◽

Vol 23 ◽

pp. ix345

Author(s):

Y. Chang ◽

N. Su ◽

Y. Leu ◽

J. Lee ◽

C. Liu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Dna Repair ◽

Clinical Outcome ◽

Cell Carcinoma ◽

Head And Neck ◽

Gene Polymorphisms ◽

Repair Gene ◽

Dna Repair Gene ◽

Recurrent Squamous Cell Carcinoma ◽

Favorable Clinical Outcome

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Downregulation of the DNA Repair Gene DDB2 by Arecoline Is through p53’s DNA-Binding Domain and Is Correlated with Poor Outcome of Head and Neck Cancer Patients with Betel Quid Consumption

Cancers ◽

10.3390/cancers12082053 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2053

Author(s):

Yu-Chu Wang ◽

Jau-Ling Huang ◽

Ka-Wo Lee ◽

Hsing-Han Lu ◽

Yuan-Jen Lin ◽

...

Keyword(s):

Dna Repair ◽

Head And Neck Cancer ◽

Dna Binding ◽

Head And Neck ◽

Neck Cancer ◽

Excision Repair ◽

Ectopic Expression ◽

Transactivation Domain ◽

Poor Outcome ◽

Dna Repair Gene

Arecoline is the principal alkaloid in the areca nut, a component of betel quids (BQs), which are carcinogenic to humans. Epidemiological studies indicate that BQ-chewing contributes to the occurrence of head and neck cancer (HNC). Previously, we have reported that arecoline (0.3 mM) is able to inhibit DNA repair in a p53-dependent pathway, but the underlying mechanism is unclear. Here we demonstrated that arecoline suppressed the expression of DDB2, which is transcriptionally regulated by p53 and is required for nucleotide excision repair (NER). Ectopic expression of DDB2 restored NER activity in arecoline-treated cells, suggesting that DDB2 downregulation was critical for arecoline-mediated NER inhibition. Mechanistically, arecoline inhibited p53-induced DDB2 promoter activity through the DNA-binding but not the transactivation domain of p53. Both NER and DDB2 promoter activities declined in the chronic arecoline-exposed cells, which were consistent with the downregulated DDB2 mRNA in BQ-associated HNC specimens, but not in those of The Cancer Genome Atlas (TCGA) cohort (no BQ exposure). Lower DDB2 mRNA expression was correlated with a poor outcome in HNC patients. These data uncover one of mechanisms underlying arecoline-mediated carcinogenicity through inhibiting p53-regulated DDB2 expression and DNA repair.

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Patients with Systemic Sclerosis Present Increased DNA Damage Differentially Associated with DNA Repair Gene Polymorphisms

The Journal of Rheumatology ◽

10.3899/jrheum.130376 ◽

2014 ◽

Vol 41 (3) ◽

pp. 458-465 ◽

Cited By ~ 11

Author(s):

Gustavo Martelli Palomino ◽

Carmen L. Bassi ◽

Isabela J. Wastowski ◽

Danilo J. Xavier ◽

Yara M. Lucisano-Valim ◽

...

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Systemic Sclerosis ◽

Blood Cells ◽

Gene Polymorphisms ◽

Peripheral Blood Cells ◽

Dna Repair Genes ◽

Repair Gene ◽

Dna Repair Gene ◽

Repair Genes

Objective.Patients with systemic sclerosis (SSc) exhibit increased toxicity when exposed to genotoxic agents. In our study, we evaluated DNA damage and polymorphic sites in 2 DNA repair genes (XRCC1Arg399Gln andXRCC4Ile401Thr) in patients with SSc.Methods.A total of 177 patients were studied for DNA repair gene polymorphisms. Fifty-six of them were also evaluated for DNA damage in peripheral blood cells using the comet assay.Results.Compared to controls, the patients as a whole or stratified into major clinical variants (limited or diffuse skin involvement), irrespective of the underlying treatment schedule, exhibited increased DNA damage.XRCC1(rs: 25487) andXRCC4(rs: 28360135) allele and genotype frequencies observed in patients with SSc were not significantly different from those observed in controls; however, theXRCC1Arg399Gln allele was associated with increased DNA damage only in healthy controls and theXRCC4Ile401Thr allele was associated with increased DNA damage in both patients and controls. Further, theXRCC1Arg399Gln allele was associated with the presence of antinuclear antibody and anticentromere antibody. No association was observed between these DNA repair gene polymorphic sites and clinical features of patients with SSc.Conclusion.These results corroborate the presence of genomic instability in SSc peripheral blood cells, as evaluated by increased DNA damage, and show that polymorphic sites of theXRCC1andXRCC4DNA repair genes may differentially influence DNA damage and the development of autoantibodies.

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