Genetic Risk Markers for Nasopharyngeal Carcinoma in Portugal: Tumor Necrosis Factor Alpha -308G>A Polymorphism

The tumor necrosis factor-alpha (TNF-alpha) is a strong proinflammatory cytokine produced by the activated macrophages in the immune response to viral infections. A common polymorphism on the promoter region of TNFA gene (-308G>A) has been associated with different susceptibilities to the development of several diseases including viral-associated neoplasias. Data suggest that the A allele has been associated with higher levels of TNF-a and, therefore, leads to increased risk of cancer development. We have performed a case-control study considering the role of the -308G>A polymorphism in 750 individuals from the northern region of Portugal, including 123 patients with nasopharyngeal carcinoma (NPC) and 627 healthy individuals. Our study revealed an increased frequency of the -308A TNFA allele in patients with NPC. The statistical analysis for recessive model revealed that -308AA genotype is associated with increased risk for the development of NPC (odds ratio=2.46; 95% confidence interval, 0.98-6.17; p=0.047); moreover, this effect was stronger in undifferentiated types, which are virtually 100% caused by the Epstein-Barr virus (odds ratio=2.75; 95% confidence interval, 1.09-6.90; p=0.025). These results reveal that in our population 308 TNFA AA genotype can represent a risk marker for NPC development and contributes for the definition of genetic susceptibility profiles for individuals at risk of development of a viral infection and associated neoplasia.