Genetic risk markers for nasopharyngeal carcinoma in Portugal: tumor necrosis factor alpha  -308G >A polymorphism.
The tumor necrosis factor-alpha (TNF-α) 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-α 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.
Sousa
Hugo
H
Molecular Oncology Group, Portuguese Institute of Oncology of Porto, Porto, Portugal. hugo.sousa@ipoporto.min-saude.pt
Breda
Eduardo
E
Santos
Alexandra M
AM
Catarino
Raquel
R
Pinto
Daniela
D
Medeiros
Rui
R
D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011174:Portugal; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014408:Biomarkers, Tumor; D014409:Tumor Necrosis Factor-alpha