A Functional Promotor Polymorphism of TNF-α Is Associated with Primary Gastric B-Cell Lymphoma

• Published in: The American journal of gastroenterology Vol. 100; no. 12; pp. 2644 - 2649
• Main Authors: HELLMIG, Stephan, FISCHBACH, Wolfgang, GOEBELER-KOLVE, Maria-Elisabeth, FÖLSCH, Ulrich Robert, HAMPE, Jochen, SCHREIBER, Stefan
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing 01-12-2005
• Subjects: Adult; Aged; Aged, 80 and over; Base Sequence; Biological and medical sciences; Case-Control Studies; Female; Follow-Up Studies; Gastroenterology. Liver. Pancreas. Abdomen; Genetic Predisposition to Disease; Genotype; Helicobacter Infections - diagnosis; Helicobacter Infections - epidemiology; Helicobacter pylori; Helicobacter pylori - isolation & purification; Hematologic and hematopoietic diseases; Humans; Incidence; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, B-Cell - epidemiology; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - physiopathology; Male; Medical sciences; Middle Aged; Molecular Sequence Data; Polymerase Chain Reaction; Polymorphism, Genetic; Probability; Prospective Studies; Reference Values; Risk Assessment; Stomach Neoplasms - epidemiology; Stomach Neoplasms - genetics; Stomach Neoplasms - physiopathology; Tumor Necrosis Factor-alpha - genetics; Stomach; Lymphoproliferative syndrome; Gastroenterology; Malignant hemopathy; Lymphoma; Tumor necrosis factor α; Polymorphism
• ISSN: 0002-9270; 1572-0241
• DOI: 10.1111/j.1572-0241.2005.00338.x

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.
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.
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.
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.