The influence of Tumor Necrosis Factor-alpha gene polymorphism on oxidative stress in patients with oral precancerous lesions and oral cancer

Objective: The aim of our study was to determine the association of Tumor Necrosis Factor alpha (TNF-alpha) single nucleotide polymorphism (SNP) characterized by the substitution of guanine (G) by adenine (A) at the position -238 (TNF-alpha-238G/A) and position -308 (TNF-alpha-308G/A) in the promoter region of TNF alpha with oral precancerous lesions and oral cancer and its influence on oxidative stress and antioxidant enzymes. Design: The study group consisted of 125 subjects were included for the study among which 40 subjects each of oral cancer and oral precancerous lesions respectively and 45 were normal healthy controls. Genotyping was done by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and antioxidant enzymes like catalase, superoxide dismutase (SOD), glutathione reductase (GR), and oxidative stress markers like malondialdehyde (MDA) were estimated in blood plasma. Results: Significant association of TNF-alpha-308G/A single nucleotide polymorphism with oral precancerous lesions and oral cancer. A significant difference in the catalase activity was observed in the TNF alpha-308GA genotype as compared to the GG genotype in oral cancer. Superoxide dismutase and glutathione reductase activity was reduced in TNF alpha-238AA subgroup of oral cancer patients and in TNF alpha-308 GA genotype in both the groups of patients. A significant increase in malondialdehyde level was observed in the TNF-alpha-238 rare genotype as compared to the homozygous wild type. Conclusion: Oxidative stress in patients with oral precancerous lesions and oral cancer correlates with the presence of TNF alpha-238AA and TNF alpha-308GA genotypes which could help in designing new therapeutic strategies for oral cancer treatment.