title: Apoptotic variants as predictors of risk of oropharyngeal cancer recurrence after definitive radiotherapy.
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.
authors.affiliation: Department of Head and Neck Surgery, the University of Texas MD Anderson Cancer Center, Houston, TX.|Department of General Surgery, Hebei General Hospital, Shijiazhuang, Hebei, China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Head and Neck Surgery, the University of Texas MD Anderson Cancer Center, Houston, TX.|Department of Epidemiology, the University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.affiliation: Department of Head and Neck Surgery, the University of Texas MD Anderson Cancer Center, Houston, TX.|Department of Otolaryngology-Head and Neck Surgery, Yuhuangding Hospital of Qingdao University, Yantai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Head and Neck Surgery, the University of Texas MD Anderson Cancer Center, Houston, TX.|Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key Laboratory of Otolaryngology Head and Neck Surgery Capital Medical University, Ministry of Education, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Head and Neck Surgery, the University of Texas MD Anderson Cancer Center, Houston, TX.|Department of Otorhinolaryngology-Head and Neck Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Head and Neck Surgery, the University of Texas MD Anderson Cancer Center, Houston, TX.|Department of Otorhinolaryngology-Head and Neck Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Head and Neck Surgery, the University of Texas MD Anderson Cancer Center, Houston, TX.|Department of Epidemiology, the University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000532:radiotherapy* / Q000821:virology; D015331:Cohort Studies; D053222:Fas Ligand Protein / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics; D009959:Oropharyngeal Neoplasms / Q000235:genetics / Q000532:radiotherapy* / Q000821:virology; D030361:Papillomavirus Infections / Q000235:genetics / Q000532:radiotherapy*; D020641:Polymorphism, Single Nucleotide; D016019:Survival Analysis; D019014:fas Receptor / Q000235:genetics*
chemical_list: C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor
keywords: FAS and FASLG; apoptosis; biomarkers; genetic variants; head and neck cancer; human papillomavirus; oropharyngeal cancer; recurrence