title: Variants in nucleotide excision repair core genes and susceptibility to recurrence of squamous cell carcinoma of the oropharynx.
abstract: 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: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
authors: Xicheng
authors: X
authors: Song
authors: Erich M
authors: EM
authors: Sturgis
authors: Lei
authors: L
authors: Jin
authors: Zhongqiu
authors: Z
authors: Wang
authors: Qingyi
authors: Q
authors: Wei
authors: Guojun
authors: G
authors: Li
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D018572:Disease-Free Survival; D004720:Endonucleases / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D052162:Human papillomavirus 16 / Q000235:genetics; D052161:Human papillomavirus 18 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D009959:Oropharyngeal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D014157:Transcription Factors; D051760:Xeroderma Pigmentosum Group A Protein; D051759:Xeroderma Pigmentosum Group D Protein; D000099250:DNA Excision Repair Protein ERCC-5; C497314:XPA protein, human; C086984:XPC protein, human; C071447:ERCC1 protein, human; C497292:ERCC2 protein, human