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Apoptotic variants as predictors of risk of oropharyngeal cancer recurrence after definitive radiotherapy.

dc.contributor.author Zhang, Fenghua
dc.contributor.author Sturgis, Erich M
dc.contributor.author Sun, Yan
dc.contributor.author Zhang, Yang
dc.contributor.author Wei, Qingyi
dc.contributor.author Zhang, Caiyun
dc.contributor.author Zheng, Hongliang
dc.contributor.author Li, Guojun
dc.coverage.spatial United States
dc.date.accessioned 2015-10-07T16:37:30Z
dc.date.issued 2015-11-15
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/25976983
dc.identifier.uri https://hdl.handle.net/10161/10674
dc.description.abstract Single nucleotide polymorphisms (SNPs) in the promoter region of FAS and FASLG may alter their transcriptional activity. Thus, we determined the associations between four FAS and FASLG promoter variants (FAS1377G>A, rs2234767; 670A>G, rs1800682; FASLG844T>C, rs763110 and 124A>G, rs5030772) and the risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP). We evaluated the associations between FAS and FASLG genetic variants and the risk of recurrence in a cohort of 1,008 patients. The log-rank test and multivariate Cox models were used to evaluate the associations. Compared with patients with common homozygous genotypes of FAS670 and FASLG844 polymorphisms, patients with variant genotypes had lower disease-free survival rates (log-rank p < 0.0001 and p < 0.0001, respectively) and an approximately threefold higher risk of SCCOP recurrence (HR, 3.2;95% CI, 2.2-4.6; and HR, 3.1; 95% CI, 2.2-4.4, respectively) after multivariate adjustment. Furthermore, among patients with HPV16-positive tumors, those with variant genotypes of these two polymorphisms had lower disease-free survival rates (log-rank, p < 0.0001 and p < 0.0001, respectively) and a higher recurrence risk than did patients with common homozygous genotypes (HR, 12.9; 95% CI, 3.8-43.6; and HR, 8.1; 95% CI, 3.6-18.6, respectively), whereas no significant associations were found for FAS1377 and FASLG124 polymorphisms. Our findings suggest that FAS670 and FASLG844 polymorphisms modulate the risk of recurrence of SCCOP, particularly in patients with HPV16-positive tumors. Larger studies are needed to validate these results.
dc.language eng
dc.publisher Wiley
dc.relation.ispartof Int J Cancer
dc.relation.isversionof 10.1002/ijc.29604
dc.subject FAS and FASLG
dc.subject apoptosis
dc.subject biomarkers
dc.subject genetic variants
dc.subject head and neck cancer
dc.subject human papillomavirus
dc.subject oropharyngeal cancer
dc.subject recurrence
dc.subject Adult
dc.subject Aged
dc.subject Aged, 80 and over
dc.subject Antigens, CD95
dc.subject Carcinoma, Squamous Cell
dc.subject Cohort Studies
dc.subject Fas Ligand Protein
dc.subject Female
dc.subject Genetic Association Studies
dc.subject Humans
dc.subject Male
dc.subject Middle Aged
dc.subject Neoplasm Recurrence, Local
dc.subject Oropharyngeal Neoplasms
dc.subject Papillomavirus Infections
dc.subject Polymorphism, Single Nucleotide
dc.subject Survival Analysis
dc.title Apoptotic variants as predictors of risk of oropharyngeal cancer recurrence after definitive radiotherapy.
dc.type Journal article
duke.contributor.id Wei, Qingyi|0632334
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/25976983
pubs.begin-page 2454
pubs.end-page 2461
pubs.issue 10
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Medical Oncology
pubs.organisational-group School of Medicine
pubs.publication-status Published
pubs.volume 137
dc.identifier.eissn 1097-0215
duke.contributor.orcid Wei, Qingyi|0000-0002-3845-9445


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