Dataset Information

Association between the rs3751143 polymorphism of P2RX7 gene and chronic lymphocytic leukemia: A meta-analysis.

ABSTRACT:

Objectives

Meta-analysis was used to determine the association between rs3751143 polymorphism of P2RX7 gene and the risk of chronic lymphocytic leukemia (CLL).

Methods

Search for published articles about the association between the rs3751143 and CLL in PubMed, MEDINE, Web of Science, and Embase databases, with a calculated odds ratio of (OR) and 95% confidence interval (95%CI).

Results

A total of 1184 cases and 1725 controls in 8 studies were pooled together for evaluation of the overall association between rs3751143 and risk of CLL. Allele model (A vs C, p = 0.16, OR = 0.85, 95%CI = 0.71-1.17), homozygous model (AA vs CC, p = 0.07; OR = 0.78, 95%CI = 0.84-1.08), and heterozygous model (AC vs CC, p = 0.76; OR = 0.85; 95%CI = 0.68-0.79) did not show decreased risk of developing CLL. Similarly, dominant model (AA + AC vs. CC: p = 0.58; OR = 1.10, 95%CI = 0.69-1.75), and recessive model (AA vs AC + CC, p = 0.21, OR = 1.18, 95%CI = 0.70-1.99) failed to show decreased risk of developing CLL. However, in familial, heterozygous model (AC vs. CC: p = 0.0006, OR = 0.64, 95%CI = 0.67-1.50) and recessive model (AA vs. AC + CC: p = 0.0017; OR = 1.02, 95%CI = 0.73-2.35) indicated the association between the inheritance of rs3751143 and the risk of developing CLL. In the overall survival prognosis, no significant association between rs3751143 and CLL was detected with relatively high heterogeneity.

Conclusions

Our pooled data indicates that there is a correlation between the inheritance of rs3751143 and the risk of CLL in familial.

SUBMITTER: Zhang WJ

PROVIDER: S-EPMC7855105 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Chronic lymphocytic leukemia (CLL) is incurable through conventional chemoimmunotherapy regimens. Despite durable responses to front-line therapy and sustained remission rates in patients with CLL, a majority of patients eventually relapse in 5 years of initial treatment. The depth of the response may affect the length of response. Maintenance therapies were aimed to deep remissions and extend the period of disease quiescence. Lenalidomide, rituximab and ofatumumab had demonstrated some efficacy as a maintenance therapy compared to no intervention for CLL patients. The relative effect on disease control and safety between different maintenance therapies were unclear. METHODS:We performed a systematic literature review and network meta-analysis to evaluate relative effect on disease control and safety of current available maintenance therapies. We searched PubMed, Embase and Cochrane database up to March 6, 2019. Relevant reference of review article and conference abstract including European Hematology Association Annual Meeting (EHA 2018), American Society of Hematology Annual Meeting (ASH 2018) and American Society of Clinical Oncology Annual Meeting (ASCO 2018) were searched. Randomized controlled trials (RCT) involving current available maintenance therapy including "Lenalidomide", "Rituximab", "Ofatumumab", "Ibrutinib", "Idelalisib", "Venetoclax"and "Obinutuzumab"were eligible. Outcomes of interest included progression-free survival (PFS), overall survival (OS) and serious adverse events (SAE) in CLL patients received subsequent maintenance therapy. Two authors CHL and CL) independently assessed eligibility for all identified citations and extracted data from the original trial reports. The selected studies' risk of bias was assessed following the guidelines of Cochrane Collaboration Handbook. RESULTS:In total, six phase III RCTs with total 1,615 CLL patients were identified. Maintenance therapy using lenalidomide, rituximab, and ofatumumab demonstrated a statistically significant effect in prolongation of progression-free survival (HR:0.37, 95% CI: 0.27-0.50 of lenalidomide; HR:0.50, 95% CI: 0.38-0.66 of rituximab; HR:0.52, 95% CI:0.41-0.66 of ofatumumab, separately) compared with no intervention; however, for overall survival, the effect of maintenance therapy showed no significant difference versus no intervention (HR: 0.89, 95% CI: 0.70-1.14). Lenalidomide showed the best efficacy for PFS (HR: 0.37, 95% CI: 0.27-0.50, Probability of being best treatment: 96%). CONCLUSIONS:Our network meta-analysis provided an integrated overview of relative efficacy and safety of different maintenance therapies in CLL. All maintenance therapies were effective in reducing the risk of disease progression versus no intervention. Based on current best evidence, maintenance therapy with lenalidomide is the most efficacious option.