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Genetic polymorphism and transcriptional regulation of CREBBP gene in patient with diffuse large B-cell lymphoma.

ABSTRACT: In the present study, we aim to examine the relationship between genetic polymorphism and transcriptional expression of cyclic AMP response element binding protein (CREBBP) and the risk of diffuse large B-cell lymphoma (DLBCL). Two hundred and fifty healthy individuals and 248 DLBCL patients participated in the present study. The CREBBP rs3025684 polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The mRNA expression of CREBBP was tested by the real-time quantitative PCR (RT-qPCR). The allele A frequency of CREBBP rs3025684 in DLBCL patients was obviously higher than that of controls (P=0.01). No significant difference was detected between CREBBP rs3025684 polymorphism and clinical characteristics of DLBCL patients when subgrouped according to different parameters. The results demonstrated that the allele A of CREBBP rs3025684 increased the susceptibility to DLBCL (P=0.004), with a worse overall survival (OS) rate (P=0.002), a worse progression-free survival (PFS) rate (P=0.033) and poor prognosis (P=0.003) in DLCBL patients. Furthermore, the expression of CREBBP mRNA was considerably decreased in DLBCL patients as compared with controls (P<0.001), and the expression in patients with GG genotype was up-regulated in comparison with patients with GA and AA genotype (P=0.016 and P=0.001, respectively). However, no statistical differences were found in OS (P=0.201) and PFS (P=0.353) between the lower CREBBP mRNA level subgroup and higher CREBBP mRNA level subgroup. These data suggested that the CREBBP gene may be an important prognostic factor in DLBCL patients and perform an essential function in the development of DLBCL.

SUBMITTER: Zhao H

PROVIDER: S-EPMC6692565 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Genetic polymorphism and transcriptional regulation of CREBBP gene in patient with diffuse large B-cell lymphoma.

Zhao Haifeng H Kan Yutian Y Wang Xinyuan X Chen Leiyuan L Ge Peng P Qian Zhengzi Z

Bioscience reports 20190813 8

In the present study, we aim to examine the relationship between genetic polymorphism and transcriptional expression of cyclic AMP response element binding protein (CREBBP) and the risk of diffuse large B-cell lymphoma (DLBCL). Two hundred and fifty healthy individuals and 248 DLBCL patients participated in the present study. The CREBBP rs3025684 polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The mRNA expression of CRE ...[more]

PMID: 31366566

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Project description:Objectivep53 gene, as "the guardian of the genome", is the most widely studied tumor suppressor gene. Previous studies have shown that about 50 percent of tumors have P53 dysfunction. This article aims to retrospectively analyze the correlation between p53 rs1625895 polymorphism and the prognosis of patients with diffuse large B-cell lymphoma (DLBCL).MethodsPCR combined with Sanger sequencing were used to detect rs1625895 genotype in 384 DLBCL patients. The relationship between rs1625895 polymorphisms and the clinical characteristics, first-line therapeutic effects and the prognosis of the patients were analyzed.ResultsAmong all the patients, 2 (0.5%) patients with AA genotype, 34 (8.9%) patients with AG genotype and 348 (90.6%) patients with GG genotype were identified. The patients with different rs1625895 genotypes did not have any difference in terms of age, gender, B symptoms (developing any of the following symptoms: unexplained recurrent fever (often above 38 °C), night sweats, and unexplained weight loss of 10% within 6 months ), erythrocyte sedimentation rate (ESR), international prognostic index (IPI) and molecular subtype (P>0.05). The overall response rate (ORR) was 82.9% and 82.8% in AA/AG and GG, respectively. There was no significant difference between the first-line therapeutic effects of the two groups (P>0.05). And there was also no difference between A allele carriers and homozygous G allele carriers for the 5-year progressionfree survival rate (PFS) (71.8% vs. 62.3%, χ2=1.351, P=0.245) and 5-year overall survival rate (OS) (72.2% vs. 64.1%, χ2=1.267, P=0.260). But in the subgroup with Germinal Center B-cell (GCB) type, the patients carrying A allele for rs1625895 had an obviously longer PFS (91.7% vs. 72.7%, χ2=4.493, P=0.034) and OS (91.7% vs. 76.7%, χ2=4.246, P=0.039) compared with the patients homozygous for the G allele. As for the patients with non-GCB subtype, there was no significant difference in PFS and OS between different rs1625895 genotypes (P>0.05). According to whether the first-line regimen contained rituximab or not, the patients were divided into two groups treated with cyclophosphoramide, doxorubicin, vincristine and prednisone (CHOP) or with rituximab and CHOP (R-CHOP). But in both subgroups, there was no significant difference in the 5-year PFS and OS between the AA/AG and GG patients, too (P>0.05).ConclusionFor DLBCL patients receiving CHOP regimen chemotherapy in the first line, p53 rs1625895 cannot predict the clinical efficacy and prognosis of the patients, but in the patients with GCB subtype, this polymorphism may be a prognostic indicator.

Dataset Information

Genetic polymorphism and transcriptional regulation of CREBBP gene in patient with diffuse large B-cell lymphoma.

Publications

Genetic polymorphism and transcriptional regulation of <i>CREBBP</i> gene in patient with diffuse large B-cell lymphoma.

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