TGF-beta1 gene polymorphisms influence the course of the disease in non-Hodgkin's lymphoma patients.
Non-Hodgkin's lymphomas (NHL) constitute a heterogenous group of mainly B-cell lymphoproliferative diseases with different patterns of clinical behaviour. Biological mechanisms leading to development of NHL are not clearly understood. Transforming growth factor-beta1 (TGF-beta1) influences B cell growth and development. The present study aimed to determine whether there is an association between the polymorphic features located within the TGF-beta1 gene in NHL patients and progression of the disease. Two single nucleotide polymorphisms at positions 869 T/C (Leu10Pro) and 915 G/C (Arg25Pro) in the precursor region of the TGF-beta1 gene were determined in 55 NHL patients and 50 healthy individuals by PCR-SSP technique using commercial primers. In univariate analysis the presence of TGF-beta1 high producer genotypes (T/T G/G or T/C G/G) was found to significantly associate with an increased number of extranodal sites (11/30 vs 3/25, p=0.035 for two or more extranodal sites in patients having or lacking the TGF-beta1 high producer genotype, respectively). TGF-beta1 high producer genotype together with other clinical and biological factors (patient sex and age, stage and aggressiveness of the disease, presence of B symptoms, serum LDH level) were subjected to multivariate logistic regression analyses for the number of extranodal sites. Multivariate analysis confirmed the role of TGF-beta1 high producer genotype as a risk factor of NHL manifestation in two or more extranodal sites (OR=7.217, p=0.043) in addition to histological aggressiveness of the disease (OR=4.302, p=0.057). TGF-beta1 gene polymorphisms were found to associate with the course of the disease in NHL patients. TGF-beta1 high producer genotype appeared as an independent risk factor of extranodal manifestation of the disease.
Mazur
Grzegorz
G
Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland.
Bogunia-Kubik
Katarzyna
K
Wrobel
Tomasz
T
Kuliczkowski
Kazimierz
K
Lange
Andrzej
A
D000483:Alleles; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1