TY - JOUR
T1 - Apoptotic variants as predictors of risk of oropharyngeal cancer recurrence after definitive radiotherapy
AU - Zhang, Fenghua
AU - Sturgis, Erich M.
AU - Sun, Yan
AU - Zhang, Yang
AU - Wei, Qingyi
AU - Zhang, Caiyun
AU - Zheng, Hongliang
AU - Li, Guojun
N1 - Publisher Copyright:
© 2015 UICC.
PY - 2015/11/15
Y1 - 2015/11/15
N2 - 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. What's new? Recurrence of squamous cell carcinoma of the oropharynx (SCCOP) may be influenced by genetic factors, the identification of which could lead to the discovery of predictive markers with the potential to improve patient outcomes. In this study, the risk of SCCOP recurrence was linked to apoptotic variants in the promoter regions of the FAS and FASLG genes. The variants were associated with reduced disease-free survival, particularly in patients who were positive for human papillomavirus. Though the mechanistic basis remains unclear, the variants may affect FAS and FASLG expression, thereby altering apoptotic responses to treatments such as radiotherapy.
AB - 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. What's new? Recurrence of squamous cell carcinoma of the oropharynx (SCCOP) may be influenced by genetic factors, the identification of which could lead to the discovery of predictive markers with the potential to improve patient outcomes. In this study, the risk of SCCOP recurrence was linked to apoptotic variants in the promoter regions of the FAS and FASLG genes. The variants were associated with reduced disease-free survival, particularly in patients who were positive for human papillomavirus. Though the mechanistic basis remains unclear, the variants may affect FAS and FASLG expression, thereby altering apoptotic responses to treatments such as radiotherapy.
KW - FAS and FASLG
KW - apoptosis
KW - biomarkers
KW - genetic variants
KW - head and neck cancer
KW - human papillomavirus
KW - oropharyngeal cancer
KW - recurrence
UR - http://www.scopus.com/inward/record.url?scp=84941943328&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84941943328&partnerID=8YFLogxK
U2 - 10.1002/ijc.29604
DO - 10.1002/ijc.29604
M3 - Article
C2 - 25976983
AN - SCOPUS:84941943328
SN - 0020-7136
VL - 137
SP - 2454
EP - 2461
JO - International journal of cancer
JF - International journal of cancer
IS - 10
ER -