Tumor necrosis factor promoter gene polymorphism associated with increased susceptibility to non‐Hodgkin's lymphomas

Abstract

The tumor necrosis factor (TNF) is a pro-inflammatory cytokine involved in the severity of different immune-regulated diseases including autoimmune, infectious, and malignant diseases. Chronic immune system stimulation could be a potential etiologic factor in these diseases. Given the determining role of TNF acting early in the immune response, we investigated the effect of an inherited genetic polymorphism at TNF promoter (-308A/G) on a predisposition to non-Hodgkin's lymphoma (NHL). The genotype distribution was determined in 194 patients with NHL and 160 age- and sex-matched population-based controls. The comparison of the -308TNF genotypes between the NHL patients and the controls showed a significant excess of A/A genotype that is previously associated with higher TNF production. Indeed, the A/A genotype is present in 7.7% of the cases, but in only 2.5% of the controls. This genotype is associated with a significant increased risk of NHL (odds ratio = 3.63, P = 0.028). These results indicate that the genetic polymorphism which could lead to an increased TNF production or a neighboring gene within the MHC region may influence the susceptibility to NHL in Tunisian population. Other epidemiologic studies carried out in both the Tunisian population and elsewhere are needed to confirm this finding.

Genetic variation in chromosomal translocation breakpoint and immune function genes and risk of non-Hodgkin lymphoma

“…Nonetheless, in one of the participating US studies [11] the TNF rs1800629 AA genotype was associated with a four-fold increased risk of T-cell lymphoma. An association between TNF rs1800629 and risk of NHL was also observed in a small study among whites in North Africa [9], but not in an Australian study [10]. The Australian study reported however that IL10 rs1800890 variant allele homozygosity conferred an 80% higher risk of DLBCL [10].…”

“…To date, the most consistent findings across studies are associations of genetic variation in the tumor necrosis factor (TNF) gene, but also in interleukin-10 (IL10), with risk of NHL [7][8][9][10][11][12][13]. The TNF gene regulates the expression of the cytokine TNF-a, which gives rise to the inflammatory response to infection.…”

Plasma Cytokines and Future Risk of Non-Hodgkin Lymphoma (NHL): A Case-Control Study Nested in the Italian European Prospective Investigation into Cancer and Nutrition

“…Recent genetic studies showed that SNPs from candidate genes, including TNF (10,(12)(13)(14); LTA (10); IL4, IL5, and IL6 (11); and IL10 (10)(11)(12)14), may be risk factors for NHL overall or for certain NHL subtypes. Our study showed evidence of a possible role of TNF-α in lymphomagenesis, particularly B-NHL.…”

“…Biological markers related to the immune system such as cytokines have been studied to explain the etiology of NHL (14)(15)(16). However, there are only few studies that have studied cytokine levels prospectively in relation to NHL risk and none have been in the general population.…”

Cytokine polymorphisms in Th1/Th2 pathway genes, body mass index, and risk of non-Hodgkin lymphoma

“…[43][44][45][46][47][48] The TNF gene regulates the expression of the cytokine TNF-␣, which gives rise to the inflammatory response to infection. Furthermore, high levels of TNF-␣ promote activation of the transcription factor nuclear factor-B, which has antiapoptotic effects on B cells.…”