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 1008 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 3-fold 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.

E2F transcription factor 2 variants as predictive biomarkers for recurrence risk in patients with squamous cell carcinoma of the oropharynx

“…The overall SCCOP recurrence rates, the 5-yr recurrence rate, and the associations between DFS and age at diagnosis, sex, ethnicity, smoking, alcohol use, comorbidity group, index cancer stage, and treatment were previously reported [2]. The median follow-up time and mean age at diagnosis among all patients, patients with SCCOP recurrence, and patients without recurrence were also previously reported [2].…”

Significance of microRNA-related variants in susceptibility to recurrence of oropharyngeal cancer patients after definitive radiotherapy

“…The median follow-up time and mean age at diagnosis among overall patients, recurrent patients, and patients without recurrence were previously reported [19]. The SCCOP recurrence types, 5-year recurrence rate, and the associations of those variables, including sex, age, ethnicity, smoking, alcohol use, comorbidity, index cancer stage, and treatment with DFS were also previously reported [19]. …”

Modifying effect of mouse double minute-2 promoter variants on risk of recurrence for patients with squamous cell carcinoma of oropharynx

“…Patient recruitment, including inclusion and exclusion criteria, has been described previously22. Overall, all patients with newly confirmed SCCOP were recruited regardless of age, sex, ethnicity, and clinical disease stages.…”

“…The study outcome was well-defined if patients were considered to be disease-free or to have disease recurrence on the date of last follow-up, disease recurrence, or death. Detailed information about event definition, follow-up, disease stage, treatment, and medical comorbidities, etc., has been described previously22. Patients were defined as “ever smokers” or “never smokers” and as “ever drinkers” and “never drinkers” as described previously22.…”

“…The associations between individual epidemiologic risk factors and clinical characteristics and outcome events were estimated using either the Student t-test for continuous variables or the χ 2 test for categorical variables. Univariate and multivariable analyses with Kaplan-Meier survival estimates, the log-rank test, and Cox proportional hazards regression were performed as described previously22. The estimates of the associations between the SNPs and recurrence risk are presented as hazard ratios (HRs) and their 95% confidence intervals (CIs).…”