A functional promotor polymorphism of TNF-alpha is associated with primary gastric B-Cell lymphoma

Abstract

Background and aims: The host genetic background to develop primary gastric B-cell lymphoma in patients with chronic Helicobacter pylori infection is unknown. Tumor necrosis factor (TNF)-alpha plays a key role in H. pylori-associated inflammation and appears to be involved in the evolution of lymphoproliferative disorders. We investigated four functional promotor polymorphisms in the TNF-alpha gene for association with the development of primary gastric B-cell lymphoma.

Patients and methods: A total of 144 lymphoma patients, 595 H. pylori-infected controls and 534 healthy blood donors were genotyped for TNF-alpha-238, -308, -857, and -1031 by Taqman technology and case-control analysis was conducted.

Results: There was no significant difference in allele and genotype frequencies in H. pylori-infected patients and healthy controls. TNF-857 T allele was found in 15.1% of patients with low-grade lymphoma and 9.1% of H. pylori-infected patients (Pearson's=5.7, p=0.017, OR=1.8, Wald 95% CI: 1.1< O.R.< 2.8). Carrier of the rare allele T had a 1.8-fold increased risk to develop low-grade lymphoma (Pearson's=5.4, p=0.021). Patients with high-grade lymphoma were significantly more frequent carriers of the TNF-857 T allele than healthy blood donors (30.9%vs 18.9%, Pearson's=4.5, p=0.033). Carriage of the T allele conferred a 1.9-fold increased risk (Wald 95% CI: 1.0<O.R.< 3.6). There were no associations found between any of the SNPs and disease progression.

Conclusion: In conclusion, our data provide further evidence for host genetic factors in the susceptibility of Caucasians to gastric B-cell lymphoma. Further studies are needed to elucidate the mechanistic role of TNF-alpha in tumorigenesis.