title: Site disparities in apoptotic variants as predictors of risk for second primary malignancy in patients with squamous cell carcinoma of the head and neck.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These results suggested that FAS/FASL polymorphisms might significantly modify SPM risk among patients with SCCHN in a tumor site-specific manner.
authors: Department of Head and Neck Surgery, Unit 1445, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. lenards@163.com.|Department of Otorhinolaryngology and Head and Neck Surgery, Yuhuangding Hospital of Qingdao University, Yantai, China. lenards@163.com.
authors: Yan
authors: Y
authors: Sun
authors: Department of Head and Neck Surgery, Unit 1445, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. yuwenbin429@qq.com.|Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing), Department of Head and Neck surgery, Peking University Cancer Hospital & Institute, Beijing, China. yuwenbin429@qq.com.
authors: Wenbin
authors: W
authors: Yu
authors: Department of Head and Neck Surgery, Unit 1445, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. esturgis@mdanderson.org.|Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. esturgis@mdanderson.org.
authors: Erich M
authors: EM
authors: Sturgis
authors: Department of Biostatistics and Human Genetics Center, University of Texas School of Public Health, 1200 Herman Pressler St, Houston, TX 77030, USA. peng.wei@uth.tmc.edu.
authors: Wei
authors: W
authors: Peng
authors: Department of Head and Neck Surgery, Unit 1445, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. leidapeng@sdu.edu.cn.|Department of Otolaryngology, Qilu Hospital, Shandong University; Key Laboratory of Otolaryngology, Ministry of Health, P.R. China, Jinan, Shandong, 250012, China. leidapeng@sdu.edu.cn.
authors: Dapeng
authors: D
authors: Lei
authors: Duke Cancer Institute, Duke University Medical Center, Durham, NC, 27710, USA. qingyi.wei@duke.edu.
authors: Qingyi
authors: Q
authors: Wei
authors: Department of Head and Neck Surgery, Unit 1445, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Songxicheng@126.com.|Department of Otorhinolaryngology and Head and Neck Surgery, Yuhuangding Hospital of Qingdao University, Yantai, China. Songxicheng@126.com.
authors: Xicheng
authors: X
authors: Song
authors: Department of Head and Neck Surgery, Unit 1445, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. gli@mdanderson.org.|Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. gli@mdanderson.org.
authors: Guojun
authors: G
authors: Li
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D053222:Fas Ligand Protein / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D012307:Risk Factors; D000077195:Squamous Cell Carcinoma of Head and Neck; D019014:fas Receptor / Q000235:genetics*
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor