PAI-1 Polymorphisms Have Significant Associations With Cancer Risk, Especially Feminine Cancer

Abstract

Background: The plasminogen activator inhibitor-1 (PAI-1) was found in many types of tumor cells, which involved in tumorigenesis. Some studies investigated the associations between PAI-1 polymorphisms and various cancers, but the results were inconsistent. So this study did a meta-analysis to assess the strength of relationship between PAI-1 and cancer. Methods: Articles that meet the requirements were searched from PubMed, EMBASE, MEDLINE, Scopus, CNKI, Wanfang and SinoMed electronic databases before June 17th 2021. Stata version 11.2 was performed to merge the odds ratios (ORs) values and calculate 95% confidence intervals (CIs). Stratified analyses were assessed on the basis of types of cancer, ethnicity and source of the control group. Heterogeneity and sensitivity analysis were tested, and publication bias was also estimated. A meta-regression analysis was applied to explore sources of heterogeneity. The false-positive report probabilities (FPRP) and the Bayesian False Discovery Probability (BFDP) test were used to assess the credibility of statistically significant associations. Results: Ultimately, in this study, 33 eligible reports were included with 9550 cases and 10431 controls for the rs1799889 polymorphism, 5 reports with 2705 cases and 3168 controls for the rs2227631 polymorphism, and 4 reports with 2799 cases and 4011 controls for the rs2227667 polymorphism. The ORs and 95% CIs showed a statistically significant relationship between rs1799889 4G>5G polymorphism and cancer risk, especially in feminine cancer. The term refers to cancers that occur in the female reproductive system, such as ovarian, breast, endometrial and cervical cancer. Moreover, there was no association observed for the PAI-1 promoter A>G polymorphism (rs2227631 and rs2227667). In further subgroup analyses of 4G>5G polymorphism (rs1799889), an increased susceptibility to cancer was observed in Caucasians group and some types of cancer groups. Conclusions: This article comes to a conclusion that the rs1799889 polymorphism might help to increase the risk of cancer; moreover, the susceptibility to feminine cancer is more evident.