Association of Polymorphisms in Tumor Necrosis Factor Alpha and Beta Genes with Increased Risk for Oral Cancer

Background: In light of the recently found contribution of inflammation-related factors to oral oncogenesis, the possible correlation of tumor necrosis factor alpha and beta genes (TNF-alpha and TNF-beta) with risk of oral cancer was investigated. Materials and Methods: DNA samples of 160 German and Greek patients with oral squamous cell carcinoma and 153 healthy controls of equivalent age, gender and ethnicity were studied. The functional polymorphisms TNF-alpha (-308 G/A) and TNF-beta (252 G/A), which affect gene expression, were investigated by restriction fragment length polymorphism analysis. Results: The frequencies of high expression A2 (-308A) TNF-alpha allele and high expression B1 (252G) TNF-beta allele were significantly increased in cancer patients compared to controls (respectively: 62.2% versus 14.7%, p<0.0001; OR 8.65, 95% CI 5.74-13.04 and 66.9% versus 15.7%, p<0.0001; OR 10.92, 95% CI 7.4-16.2). Three combined TNF-alpha/TNF-beta genotypes (A2A2/B1B1, A1A2/B1B2, A1A2/B1B1) were over-represented in cancer patients (p<0.001). No significant differences in allele frequencies were detected among most subgroups of patients divided in regard to cancer stage, family history for cancer or thrombosis, smoking or heavy alcohol consumption habits. Conclusion: This study showed a strong association of TNF-alpha and TNF-beta high expression alleles with increased risk of oral cancer. These findings are in accordance with previously observed high TNF-alpha levels in serum of patients with oral cancer in comparison to healthy controls.