| Objective:BCL-2 Associated X(BAX)is an important modulator of apoptosis.The associations between BAX gene polymorphism and cancer susceptibility and prognosis in different ethnic and types of cancer groups have yielded controversial results.To reconcile the results,a systematic review followed by meta-analysis was necessary to be performed.Methods:1.A systematic search of Medline,EMBASE,Cochrane library,China Biology Medicine disc(CBMdisc),CNKI,VIP,Wanfang databases for publications on BAX polymorphisms and susceptibility and prognosis was carried out until July 2017.2.Documents selection was strictly according to the inclusion criteria and exclusion criteria.Case-control studies associated with susceptibility and retrospective studies related to prognosis were screened out,and then extracted data from those included.The quality of studies in meta-analysis were assessed according to the Nescastle-Ottawa(NOS).3.The pooled ORs with 95%CIs were calculated for each gene model(allelic model A vs G,dominant model AA+GA vs GG,implicit model AA vs GA+GG,additive model AA vs GG)to measure the strength of correlation between BAX gene polymorphisms and cancer susceptibility.Subgroup analyses were performed according to ethnicity(Caucasian and Asian subgroups)and population sources(population based and hospital based subgroups).4.We assessed the effect of BAX polymorphisms on prognosis by HR.For each study,the HR and its 95%CI of the dominant gene model(AG/AA vs GG)were retrieved.5.Summary odds ratios(ORs)and hazard ratios(HRs)were combined using fixed or random-effects models as appropriate to determine the association.Publication bias was tested by visual inspection of symmetry funnel plots and formally assessed by Begg's funnel plot and Egger's test.One-way sensitivity analysis by eliding an individual study in sequence was used to confirm the stability of our findings.Results: 1.A total of twelve trials involving 3321 cases and 3209 controls were included in our pooled analysis regarding the polymorphisms associated with the susceptibility of cancers.(1)Overall,results of the present meta-analysis demonstrated there was no significant association between BAX polymorphisms and susceptibility of cancers(OR= 1.052,95%CI: 0.827-1.339,PZ=0.679,A vs G).(2)There was no relevance with cancer susceptibility even in a stratified analysis by ethnicity and the sources of control groups in overall cancer(Caucasian: OR=1.082,95%CI: 0.942-1.242,PZ=0.264,A vs G;Asian: OR=0.904,95%CI: 0.429-1.908,PZ=0.792,A vs G;PB:OR= 1.120,95%CI:0.809-1.551,PZ= 0.494,A vs G;HB: OR=1.003,95%CI: 0.834-1.205,PZ=0.979,A vs G).2.Four retrospective studies of 549 cases qualified for meta-analysis were identified to set forth the associations of the polymorphisms with cancer prognosis.Our results suggested that BAX gene polymorphisms was significantly associated with unfavorable OS(HR=1.735,95%CI:1.368-2.202,P=0.000,GG vs GA/AA).Conclusion: There is no significant association between BAX gene polymorphism and cancer susceptibility,but it probably contributes to increased adverse prognosis to cancer.The reliability of the conclusions was restricted by the limited studies.Multicenter and prospective studies should be performed to verify the clinical value of BAX gene polymorphisms on cancer susceptibility and prognosis in the future. |
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