Document Detail


Variants in nucleotide excision repair core genes and susceptibility to recurrence of squamous cell carcinoma of the oropharynx.
MedLine Citation:
PMID:  23335232     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Genetically determined capacity for NER may modulate both cancer risk and prognosis. Thus, we evaluated associations of seven selected variants in the NER core genes with recurrence risk in 658 squamous cell carcinoma of the oropharynx (SCCOP) patients treated principally by radiation. The seven polymorphisms in the core NER genes (XPC-rs2228000, XPC-rs2228001, XPD-rs1799793, XPD-rs13181, XPG-rs17655, ERCC1-rs3212986 and XPA-rs1800975) were genotyped using PCR-RFLP method and log-rank test and multivariable Cox models were used to evaluate the associations in both dominant and recessive genetic models. In a dominant model, we found that polymorphisms of XPC-rs2228000, XPD-rs1799793 and XPG-rs17655 were significantly associated with disease-free survival (log-rank, p = 0.014; p = 0.00008; p = 0.0007, respectively), and these polymorphisms were significantly associated with recurrence risk of SCCOP (hazard ratio (HR) = 1.6, 95% confidence interval (CI) 1.1-2.3 for XPC-rs2228000; HR = 0.4, 95% 0.3-0.6 for XPD-rs1799793 and HR = 0.5, 95% CI 0.4-0.8 for XPG-rs17655) after multivariable adjustment. Moreover, the borderline significant or significant associations were also found for these three polymorphisms in HPV16/18-positive SCCOP patients (HR = 1.6, 95% CI 1.0-4.1 for XPC-rs2228000; HR = 0.2, 95% CI 0.1-0.5 for XPD-rs1799793 and HR = 0.1, 95% CI 0.0-0.9 for XPG-rs17655). However, similarly significant associations were not found for these polymorphisms in a recessive model. These findings suggest that polymorphisms of XPC-rs2228000, XPD-rs1799793 and XPG-rs17655 in the NER core genes may contribute to recurrence risk of SCCOP, particularly HPV-positive SCCOP, in a dominant but not in a recessive model. However, validation of these results is warranted.
Authors:
Xicheng Song; Erich M Sturgis; Lei Jin; Zhongqiu Wang; Qingyi Wei; Guojun Li
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-02-25
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  133     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-05-22     Completed Date:  2013-07-25     Revised Date:  2014-08-05    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  695-704     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 UICC.
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MeSH Terms
Descriptor/Qualifier:
Carcinoma, Squamous Cell / epidemiology,  genetics*
DNA Repair / genetics*
DNA-Binding Proteins / genetics
Disease-Free Survival
Endonucleases / genetics
Female
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Human papillomavirus 16 / genetics
Human papillomavirus 18 / genetics
Humans
Male
Middle Aged
Neoplasm Recurrence, Local / genetics*
Nuclear Proteins / genetics
Oropharyngeal Neoplasms / epidemiology,  genetics*
Polymorphism, Single Nucleotide
Risk
Survival Analysis
Transcription Factors / genetics
Xeroderma Pigmentosum Group A Protein / genetics
Xeroderma Pigmentosum Group D Protein / genetics
Grant Support
ID/Acronym/Agency:
CA133099/CA/NCI NIH HHS; K07 CA133099/CA/NCI NIH HHS; R01 ES-11740/ES/NIEHS NIH HHS; R03 CA135679/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA excision repair protein ERCC-5; 0/DNA-Binding Proteins; 0/Nuclear Proteins; 0/Transcription Factors; 0/XPA protein, human; 0/Xeroderma Pigmentosum Group A Protein; 156533-34-5/XPC protein, human; EC 3.1.-/ERCC1 protein, human; EC 3.1.-/Endonucleases; EC 3.6.4.12/Xeroderma Pigmentosum Group D Protein; EC 5.99.-/ERCC2 protein, human
Comments/Corrections

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