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Journal of Peking University(Health Sciences) ›› 2019, Vol. 51 ›› Issue (5): 791-796. doi: 10.19723/j.issn.1671-167X.2019.05.001

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Relationship between p53 rs1625895 polymorphism and prognosis in diffuse large B-cell lymphoma

Yan TIAN1,Jun ZHU2,△()   

  1. 1. Department of Medical Oncology, Peking University First Hospital, Beijing 100009, China
    2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education); Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing 100142, China
  • Received:2018-06-26 Online:2019-10-18 Published:2019-10-23
  • Contact: Jun ZHU E-mail:zhu-jun2017@outlook.com

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Abstract:

Objective: p53 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). Methods: PCR 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. Results: Among 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 ℃), 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%, χ 2 = 1.351, P=0.245) and 5-year overall survival rate (OS) (72.2% vs. 64.1%, χ 2 = 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%, χ 2 = 4.493,P = 0.034) and OS (91.7% vs. 76.7%, χ 2 = 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). Conclusion: For 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.

Key words: Diffuse large B-cell lymphoma, p53 gene, Single nucleotide polymorphism

CLC Number: 

  • R730.5

Table 1

DLBCL patients’ characteristics and their correlations with the genotype of rs1625895"

Clinical parameters n Genotype χ2 P
AA/AG GG
Age/years
≤60 241 22 219 0.046 0.830
>60 143 14 129
Gender
Male 197 18 179 0.027 0.870
Female 187 18 169
Subtype (no data were available for 39 patients)
GCB 102 13 89 1.693 0.193
Non-GCB 243 20 223
Ki67 (no data were available for 27 patients)
≤75% 171 16 155 0.062 0.803
>75% 186 16 170
Stage (no data were available for 1 patient)
Ⅰ-Ⅱ 178 19 159 0.635 0.426
Ⅲ-Ⅳ 205 17 188
B symptoms
Negative 252 25 227 0.257 0.612
Positive 132 11 121
ECOG score
0-1 344 32 312 0.021 0.886
2-3 40 4 36
IPI score
0-2 270 26 244 0.069 0.792
3-5 114 10 104
LDH (no data were available for 2 patients)
≤240/ IU/L 221 22 199 0.173 0.677
>240/ IU/L 161 14 147
β2-MG (no data were available for 15 patients)
Negative 272 28 244 0.789 0.374
Positive 97 7 90
ESR (no data were available for 14 patients)
Negative 162 12 150 0.810 0.368
Positive 208 21 187
Treatment
CHOP 118 11 107 0.001 0.981
R-CHOP 266 25 241

Table 2

Clinical response to CHOP therapy according to the genotype of rs1625895"

Response n Genotype χ2 P
AA/AG, n(%) GG, n(%)
Grouped by CR
PR+SD+PD 160 12(34.3) 148(43.1) 1.022 0.312
CR 218 23(65.7) 195(56.9)
Grouped by OR
PD+SD 65 6(17.1) 59(17.2) 0.000 0.993
OR(CR+PR) 313 29(82.9) 284(82.8)

Table 3

Cox multivariate analysis of prognosis of patients with DLBCL"

Variable B SE Wald df P HR 95%CI
Subtype(non-GCB vs. GCB) 0.546 0.244 4.997 1 0.025 1.727 1.070-2.787
Response(CR vs. PR+SD+PD) -1.593 0.216 54.159 1 <0.001 0.203 0.133-0.311
B symptoms(positive vs. negative) 0.424 0.194 4.810 1 0.028 1.529 1.046-2.234
β2-MG(positive vs. negative) 0.637 0.198 10.356 1 0.001 1.890 1.283-2.785
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