Tumor Necrosis Factor Gene Polymorphisms in Tunisian Patients with Non-Small Cell Lung Cancer

Abstract

Lung cancer (LC) is one of the most lethal malignant disorders; it is generally divided into two groups: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). In our present study we have been interested to NSCLC. Several approaches were adopted to study the etiology or pathophysiology of this disease. As recent reports have focused on the genetic susceptibility to this disease, with many candidate genes studied, we chose TNF in view of the major role it plays in the immune pro inflammatory system and its association with increased risk of a variety of human cancers. We have investigated three polymorphisms in the promoter region of the TNFalpha gene (-308 G/A and -238 G/A) and TNFbeta + 252A > G for their susceptibility to non-small cell lung cancer (NSCLC) in Tunisian population. We compared the distribution of these polymorphisms between 133 NSCLC patients and 174 healthy controls using a polymerase chain reaction restriction fragment length-polymorphism (PCR-RFLP) analysis. The frequencies of the two TNFalpha (-238 and -308) "A" alleles were significantly higher in NSCLC patients than in healthy controls respectively (p = 0.01; OR = 1.92; 95% CI 1.14 - 3.23 and p = 0.0000008; OR = 3.65; 95% CI 2.12 - 6.30), whereas the frequency of the TNFbeta + 252 G allele was approximately similar in the two compared groups. This study supports a relationship between TNFalpha -238G/A and TNFalpha -308G/A polymorphisms and the susceptibility to lung cancer. Contrary to other studies, the -308 A and -238A alleles have an inductive action on lung cancer development and progression in our Tunisian population. This study indicates that the TNFalpha -308G > A and TNFalpha -238G > A would be associated with increased susceptibility to lung cancer but no significant association was found in TNFbeta + 252A > G polymorphism.