机构：[1]Department of Stomatology, Jinling Hospital, School of Medicine, Nanjing University, Southern Medical University, Nanjing 210002, China.[2]Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.[3]Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.[4]Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.首都医科大学附属同仁医院[5]Department of Otorhinolaryngology and Head and Neck Surgery, Yuhuangding Hospital of Qingdao University, Yantai 264000, China.[6]Department of Head & Neck Surgery, Sichuan Cancer Hospital & institute, Chengdu, Sichuan 610041, China.四川省肿瘤医院
Background: Tumor necrosis factor alpha (TNF-alpha) plays an important role in inflammation, immunity, and defense against infection and clearance of human papillomavirus (HPV). Thus, genetic variants may modulate individual susceptibility to HPV-associated oral squamous cell carcinoma (OSCC). Methods: In this study we genotyped four common single nucleotide polymorphisms (SNPs) in the TNF-alpha promoter [ -308G > A(rs1800629), -857C > T (rs1799724), -863C > A (rs1800630), and -1031T > C (rs1799964)] and determined HPV16 serology in 325 OSCC cases and 335 matched controls and tumor HPV status in 176 squamous cell carcinomas of the oropharynx (SCCOP) patients. Univariate and multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: We found that HPV16 seropositivity alone was associated with an increased risk of OSCC (OR, 3.1; 95% CI, 2.1-4.6), and such risk of HPV16-associated OSCC was modified by each SNP. Patients with both HPV16 seropositivity and variant genotypes for each SNP had the highest risk when using patients with HPV16 seronegativity and a wild-type genotype as a comparison group. Moreover, similar results were observed for the combined risk genotypes of four variants and all such significant associations were more pronounced in several subgroups, particularly in SCCOP patients and never smokers. Notably, the combined risk genotypes of four variants were also significantly associated with tumor HPV-positive SCCOP. Conclusion: Taken together, these results suggest that TNF-alpha SNPs may individually or, more likely, jointly affect individual susceptibility to HPV16-associated OSCC, particularly SCCOP and never smokers. Validation of our findings is warranted.
基金：
National Institute of Environmental Health Sciences Grant R01 ES-11740 (to Q.W.);
N.I.H. Grant P-30 CA 16672 (to the University of Texas M.D. Anderson Cancer
Center); and N.I.H. grant CA 135679 (to G.L.) and CA133099 (to G.L.).
第一作者机构：[1]Department of Stomatology, Jinling Hospital, School of Medicine, Nanjing University, Southern Medical University, Nanjing 210002, China.[2]Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
共同第一作者：
通讯作者：
通讯机构：[2]Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.[3]Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
推荐引用方式(GB/T 7714)：
Lei Jin,Erich M Sturgis,Yang Zhang,et al.Association of tumor necrosis factor-alpha promoter variants with risk of HPV-associated oral squamous cell carcinoma[J].MOLECULAR CANCER.2013,12:doi:10.1186/1476-4598-12-80.
APA：
Lei Jin,Erich M Sturgis,Yang Zhang,Zhigang Huang,Xicheng Song...&Guojun Li.(2013).Association of tumor necrosis factor-alpha promoter variants with risk of HPV-associated oral squamous cell carcinoma.MOLECULAR CANCER,12,
MLA：
Lei Jin,et al."Association of tumor necrosis factor-alpha promoter variants with risk of HPV-associated oral squamous cell carcinoma".MOLECULAR CANCER 12.(2013)
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