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Human leukocyte antigen‐ G polymorphisms influence the clinical outcome in diffuse large B ‐cell lymphoma
Author(s) -
Bielska Marta,
Bojo Marcin,
KlimkiewiczWojciechowska Gabriela,
JesionekKupnicka Dorota,
Borowiec Maciej,
KalinkaWarzocha Ewa,
ProchorecSobieszek Monika,
Robak Tadeusz,
Warzocha Krzysztof,
Młynarski Wojciech,
LechMaranda Ewa
Publication year - 2015
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22235
Subject(s) - genotype , human leukocyte antigen , lymphoma , immunology , hla g , immune system , diffuse large b cell lymphoma , biology , medicine , antigen , gastroenterology , gene , genetics
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. © 2015 Wiley Periodicals, Inc.