The gene family and gene are inextricably linked to an elevated risk of cancer development. This systemic review and meta-analysis seeks to establish the relationship between (rs11064, rs1045241, rs1045242, and rs3813308), (rs1060555), and (rs710100 and rs8126) polymorphisms with the risk of cancer. A systematic search of multiple databases from January 2022 to April 2022 was used to identify relevant studies. Odds ratios (ORs) with corresponding 95% CI and -value were calculated to assess the association. Bonferroni correction was performed to correct -values. Trial sequential analysis (TSA) and messenger RNA expression were also performed. Review Manager 5.4 software was used for performing this meta-analysis. This study comprised 6909 cancer patients and 7087 healthy participants from 14 studies. Four genetic models of rs11064 (codominant 2 [COD2]: OR = 2.30,  = 7.83 × 10; codominant 3 [COD3]: OR = 2.10,  = .0006; recessive model [RM]: OR = 2.24,  = .0001; AC: OR = 1.47,  = .037), two genetic models of rs1045241 (codominant 1 [COD1]: OR = 1.27,  = .009; overdominant model [ODM]: OR = 1.24,  = .018), four genetic models of rs1045242 (COD1: OR = 1.52,  = .005; dominant model (DM): OR = 1.56,  = .002; OD: OR = 1.48,  = .008; AC: OR = 1.48,  = .002), and three genetic models of rs8126 (COD2: OR = 1.41,  = .0005; COD3: OR = 1.44,  = .0002; RM: OR = 1.43,  = .0001) were statistically linked to cancer risk. Only one genetic model of rs1060555 polymorphism showed a significant protective association with cancer (COD2: OR = 0.80,  = .048). The outcomes of TSA also validated the findings of the meta-analysis. This study summarizes that rs11064, rs1045241, and rs1045242 polymorphisms of gene and rs8126 polymorphism of gene are significantly linked with the risk of cancer development. This meta-analysis was registered at INPLASY (registration number: INPLASY202270073).