title: The -308G/A polymorphism of the tumor necrosis factor-alpha gene is associated with the risk of upper aerodigestive tract cancer: a meta-analysis.
abstract: 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.
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, P.R. China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Jiantang
authors.initials: J
authors.lastname: Yang
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xin
authors.initials: X
authors.lastname: Zeng
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.forename: Ga
authors.initials: G
authors.lastname: Liao
authors.forename: Hongxia
authors.initials: H
authors.lastname: Dan
authors.forename: Qianming
authors.initials: Q
authors.lastname: Chen
mesh_terms: D044466:Asian People / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000208:ethnology / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D016017:Odds Ratio; D010610:Pharyngeal Neoplasms / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics
chemical_list: D014409:Tumor Necrosis Factor-alpha