title: Human leukocyte antigen-G polymorphisms influence the clinical outcome in diffuse large B-cell lymphoma.
abstract: The role of HLA-G is extensively studied in cancer due to its inhibition of the immune response. Several polymorphisms in the HLA-G gene have been reported to significantly affect its expression. We, therefore, investigated whether functionally relevant HLA-G polymorphisms, HLA-G-725C/G/T, and HLA-G 14-base pair, have any influence on the susceptibility to diffuse large B-cell lymphoma (DLBCL) and its clinical course. The polymorphisms were genotyped in 207 previously untreated patients with DLBCL and 150 unrelated controls. A significant difference in genotype distribution of HLA-G polymorphic genotypes between the patients and controls was found. The frequencies of the HLA-G-725GG or the HLA-G-725GC genotype were lower, and those of the HLA-G ins/ins genotype were higher in the patients compared with the controls. Patients carrying the HLA-G-725CC genotype presented a higher probability of overall survival (OS) than subjects with other genotype combinations of HLA-G-725C/G/T (P = 0.003). The homozygous HLA-G del/del had a lower probability of OS than subjects carrying the HLA-G deletion/insertion (del/ins) or the HLA-G ins/ins genotype (P = 0.009). Two HLA-G genotype-based risk groups were defined according to the genotype distribution. The high-risk (HR) group presented a shorter OS than low-risk (LR) patients (P = 0.001). In a multivariate analysis adjusted for International Prognostic Index (IPI) factors, both the intermediate high/high IPI-risk group (P < 0.0001) and the HR genotype group (P = 0.004) independently increased the risk of death. This is the first study indicating an important role of HLA-G polymorphisms for the clinical course of DLBCL. The potential influence of HLA-G polymorphisms on the susceptibility to DLBCL thus deserves further study.
authors.affiliation: Department of Pediatrics, Oncology, Hematology, and Diabetology, Medical University of Lodz, Lodz, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Bielska
authors.forename: Marcin
authors.initials: M
authors.lastname: Bojo
authors.forename: Gabriela
authors.initials: G
authors.lastname: Klimkiewicz-Wojciechowska
authors.forename: Dorota
authors.initials: D
authors.lastname: Jesionek-Kupnicka
authors.forename: Maciej
authors.initials: M
authors.lastname: Borowiec
authors.forename: Ewa
authors.initials: E
authors.lastname: Kalinka-Warzocha
authors.forename: Monika
authors.initials: M
authors.lastname: Prochorec-Sobieszek
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Warzocha
authors.forename: Wojciech
authors.initials: W
authors.lastname: Młynarski
authors.forename: Ewa
authors.initials: E
authors.lastname: Lech-Maranda
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D059951:HLA-G Antigens / Q000235:genetics*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D011110:Polymorphism, Genetic
chemical_list: D059951:HLA-G Antigens