Site disparities in apoptotic variants as predictors of risk for second primary malignancy in patients with squamous cell carcinoma of the head and neck.
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FAS/FASL promoter variants are considered in altering transcriptional activity of those genes and consequently alter regulation of cell death. However, no studies have investigated whether tumor sites contribute to the association between FAS/FASL polymorphisms and risk for second primary malignancy (SPM).In this study, FAS670 A > G, FAS1377 G > A, FASL124 A > G, and FASL844C > T polymorphisms were genotyped in 752 OPC and 777 non-OPC patients. Both univariate and multivariable cox proportional hazard models were used to assess the associations.The univariate and multivariable analyses showed that patients with index OPC and FASL844 CT/TT genotype had significantly increased risk of SPM (cHR, 2.5; 95% CI, 1.1-5.8, P = 0.043 and aHR, 2.7; 95% CI, 1.2-6.0, P = 0.032) compared with those with FASL844 CC genotype as the reference group, while index non-OPC patients with FAS670 AG/GG and FasL844 CT/TT genotypes had significantly increased risk of SPM (cHR, 2.2 and 1.8; 95% CI, 1.2-5.7 and 1.1-3.2; and P = 0.04 and 0.041, respectively and aHR, 2.4 and 1.7; 95% CI, 1.1-5.1 and 1.0-3.0; and P = 0.043 and 0.049, respectively) compared with their corresponding AA and CC genotypes . Moreover, patients carrying more FAS/FASL variants significantly increased risk of SPM among index non-OPC patients. The stratified analysis showed that smoking status differently modified the associations between FAS/FASL polymorphisms and risk of SPM among index non-OPC from OPC patients.These results suggested that FAS/FASL polymorphisms might significantly modify SPM risk among patients with SCCHN in a tumor site-specific manner.
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Second Primary
Proportional Hazards Models
Fas Ligand Protein
Promoter Regions, Genetic
Genetic Association Studies
Published Version (Please cite this version)10.1186/s12885-016-2110-y
Publication InfoSun, Yan; Yu, Wenbin; Sturgis, Erich M; Peng, Wei; Lei, Dapeng; Wei, Qingyi; ... Li, Guojun (2016). Site disparities in apoptotic variants as predictors of risk for second primary malignancy in patients with squamous cell carcinoma of the head and neck. BMC cancer, 16(1). pp. 70. 10.1186/s12885-016-2110-y. Retrieved from https://hdl.handle.net/10161/18026.
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Professor in Population Health Sciences
Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally recognized epidemiologist focused on the molecular and genetic epidemiology of head and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and genetic determinants for the DNA repair deficient phenotype and