Tohoku J. Exp. Med., 2013 April, 229(4)

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

JIAYI WANG,¹ XIN JIN,¹ HUI WANG,² JIANTANG YANG,³ LILI WANG,¹ LEI LEI,¹ XIAOXU LI,¹ YU ZHOU,¹ XIN ZENG,¹ LU JIANG,¹ GA LIAO,¹ HONGXIA DAN¹ and QIANMING CHEN¹

¹State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, P.R. China
²Department of Oral Medicine, School of Stomatology, Capital Medical University, Beijing, P.R. China
³Stomatological Hospital, Zunyi Medical College, Zunyi, Guizhou, P.R. China

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.

keywords —— epidemiology; gene polymorphism; meta-analysis; tumor necrosis factor-alpha; upper aerodigestive tract cancer

© 2013 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2013, 229, 245-254

Correspondence: Ga Liao and Hongxia Dan, State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China.

e-mail: liaoga@gmail.com (Ga Liao), hxdan@foxmail.com (Hongxia Dan).