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Genetic variants in TNF-alpha promoter are predictors of recurrence in patients with squamous cell carcinoma of oropharynx after definitive radiotherapy

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机构: [1]Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX [2]Department of Otorhinolaryngology-Head and Neck Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China [3]Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX [4]Department of Otolaryngology-Head and Neck Surgery, Yuhuangding Hospital of Qingdao University, Yantai, China [5]Division of Biostatistics and Human Genetics Center, University of Texas School of Public Health, Houston, TX [6]Department of Stomatology, Jinling Hospital, School of Medicine, Nanjing University, Southern Medical University, Nanjing, China [7]Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu, China
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关键词: TNF- variant recurrence genetic polymorphisms biomarkers human papillomavirus head and neck cancer oropharyngeal cancer

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The promoter variants of TNF-, a major regulator of immune and inflammation responses, have been implicated in cancer development and prognosis. Thus, we investigated associations between four TNF- promoter variants and risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP). We evaluated associations of four TNF- polymorphisms with risk of recurrence in a cohort of 846 patients with SCCOP. Log-rank test and multivariable Cox models were used to evaluate associations. Compared with patients with variant genotypes of the TNF- -308 and TNF- -863 polymorphisms, patients with common homozygous genotypes had worse disease-free survival (log-rank p = 0.0002 and p < 0.0001, respectively) and increased risk of SCCOP recurrence (HR, 1.9, 95% CI, 1.3-2.8 and HR, 1.9, 95% CI, 1.3-2.7, respectively) after multivariable adjustment. Furthermore, among patients with HPV16-positive tumors, those with common homozygous genotypes of the TNF- -308 and -863 polymorphisms had worse disease-free survival (log-rank p = 0.005 and p = 0.007, respectively) and higher recurrence risk than patients with variant genotypes of these polymorphisms (HR, 5.1, 95% CI, 1.4-18.4 and HR, 3.7, 95% CI, 1.5-9.1, respectively), while no such significant associations were found for TNF- -857 or -1031 polymorphisms. Our findings suggest that TNF- -308 and -863 polymorphisms may modulate the risk of SCCOP recurrence in patients with HPV16-positive tumors. However, larger studies are needed to validate these results.

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基金编号: NIH

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出版当年[2014]版:
大类 | 2 区 医学
小类 | 2 区 肿瘤学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 肿瘤学
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出版当年[2014]版:
Q1 ONCOLOGY
最新[2023]版:
Q1 ONCOLOGY

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第一作者机构: [1]Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX [2]Department of Otorhinolaryngology-Head and Neck Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China
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通讯机构: [1]Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX [3]Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX [*1]Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1445, Houston, Texas 77030-4009, USA
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