The -308G/A Polymorphism of the Tumor Necrosis Factor-alpha Gene Is Associated with the Risk of Upper Aerodigestive Tract Cancer: A Meta-analysis

• Published in: The Tohoku Journal of Experimental Medicine Vol. 229; no. 4; pp. 245 - 254
• Main Authors: Wang, Jiayi, Jin, Xin, Wang, Hui, Yang, Jiantang, Wang, Lili, Lei, Lei, Li, Xiaoxu, Zhou, Yu, Zeng, Xin, Jiang, Lu, Liao, Ga, Dan, Hongxia, Chen, Qianming
• Format: Journal Article
• Language: English
• Published: Japan Tohoku University Medical Press 01.04.2013
• Subjects: Asian Continental Ancestry Group - genetics; Carcinoma, Squamous Cell - ethnology; Carcinoma, Squamous Cell - genetics; epidemiology; European Continental Ancestry Group - genetics; Gene Expression Regulation - genetics; gene polymorphism; Genetic Predisposition to Disease - genetics; Humans; meta-analysis; Odds Ratio; Pharyngeal Neoplasms - ethnology; Pharyngeal Neoplasms - genetics; Polymorphism, Single Nucleotide - genetics; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; upper aerodigestive tract cancer
• ISSN: 0040-8727; 1349-3329
• DOI: 10.1620/tjem.229.245

Tumor necrosis factor-alpha (TNF-α) has been proposed to contribute to the development of upper aerodigestive tract (UADT) cancer that is characterized by poor prognosis. The G-to-A nucleotide change at -308 of the TNF-α gene (-308G/A polymorphism) can increase the expression level of TNF-α and thus may affect the genetic susceptibility of UADT cancer. The association between the -308G/A polymorphism and UADT cancer has been widely studied, but the results published are quite controversial. To obtain a more precise conclusion, we performed a meta-analysis including 1,751 patients and 3,345 controls. The results indicated that the AA genotype of the -308G/A polymorphism had a 54%-increased risk of UADT cancer, compared with the G carriers (GG and GA genotypes) [odds ratio (OR) = 1.54, 95% confidence interval (CI): 1.07-2.21]. After stratified by ethnicity, the AA genotype was associated with increased risk of UADT cancers in South Asians (OR = 33.18 and 95% CI: 1.92-573.62 for AA vs. GA+GG) but not in Caucasians or East Asians. After stratified by tumor site, the -308G/A polymorphism was associated with increased risks of oropharynx cancer (OR = 2.68 and 95% CI: 1.34-5.35 for AA vs. GA+GG) but not associated with esophagus or larynx cancer. After stratified by histological type, the -308G/A polymorphism was associated with increased risks of squamous cell carcinoma (OR = 1.81 and 95% CI: 1.15-2.84 for AA vs. GA+GG) but not associated with adenocarcinoma. Our results indicate that the -308G/A polymorphism might contribute to an increased risk of UADT cancer susceptibility.