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


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.


CONCLUSIONS
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.
Hellmig
Stephan
S
Department of General Internal Medicine, University Clinics of Schleswig-Holstein, Campus Kiel, Germany.
Fischbach
Wolfgang
W
Goebeler-Kolve
Maria-Elisabeth
ME
Fölsch
Ulrich Robert
UR
Hampe
Jochen
J
Schreiber
Stefan
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016481:Helicobacter Infections / Q000175:diagnosis* / Q000453:epidemiology; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D015994:Incidence; D016393:Lymphoma, B-Cell / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011336:Probability; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha