Bielska Marta, Bojo Marcin, Klimkiewicz-Wojciechowska Gabriela, Jesionek-Kupnicka Dorota, Borowiec Maciej, Kalinka-Warzocha Ewa, Prochorec-Sobieszek Monika, Robak Tadeusz, Warzocha Krzysztof, Młynarski Wojciech, Lech-Maranda Ewa
Department of Pediatrics, Oncology, Hematology, and Diabetology, Medical University of Lodz, Lodz, Poland.
Genes Chromosomes Cancer. 2015 Mar;54(3):185-93. doi: 10.1002/gcc.22235.
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.
由于HLA - G具有免疫反应抑制作用，其在癌症中的作用得到了广泛研究。据报道，HLA - G基因中的几种多态性会显著影响其表达。因此，我们研究了功能相关的HLA - G多态性，即HLA - G - 725C/G/T和HLA - G 14碱基对，是否对弥漫性大B细胞淋巴瘤（DLBCL）的易感性及其临床病程有任何影响。对207例未经治疗的DLBCL患者和150例无关对照进行了多态性基因分型。发现患者与对照之间HLA - G多态性基因型的基因型分布存在显著差异。与对照相比，患者中HLA - G - 725GG或HLA - G - 725GC基因型的频率较低，而HLA - G ins/ins基因型的频率较高。携带HLA - G - 725CC基因型的患者总生存期（OS）高于具有其他HLA - G - 725C/G/T基因型组合的受试者（P = 0.003）。纯合HLA - G del/del的OS概率低于携带HLA - G缺失/插入（del/ins）或HLA - G ins/ins基因型的受试者（P = 0.009）。根据基因型分布定义了两个基于HLA - G基因型的风险组。高风险（HR）组的OS比低风险（LR）患者短（P = 0.001）。在针对国际预后指数（IPI）因素进行调整的多变量分析中，中高/高IPI风险组（P < 0.0001）和HR基因型组（P = 0.004）均独立增加了死亡风险。这是第一项表明HLA - G多态性对DLBCL临床病程具有重要作用的研究。因此，HLA - G多态性对DLBCL易感性的潜在影响值得进一步研究。
