Flap endonuclease 1 polymorphisms (rs174538 and rs4246215) contribute to an increased cancer risk: Evidence from a meta-analysis

Flap endonuclease-1 (FEN1) is a key factor during the maintenance of genomic stability and protection against tumorigenesis. Since the identification of functional polymorphisms of FEN1 (rs174538 and rs4246215), numerous studies have evaluated the association between the two single-nucleotide polymorphisms and cancer risk. To derive a more precise estimation, a meta-analysis was performed on the association between the FEN1 polymorphisms (rs174538 and rs4246215) and cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of the associations. Thirteen case-control studies, including 5,108 cases and 6,382 case-free controls, were identified. For rs174538, individuals with the GG or GA genotype had an increased risk of cancer when compared to the -69AA genotype (AA vs. GG: OR, 1.85; 95% CI, 1.65-2.08; P<0.00001; AA vs. GA: OR, 1.43; 95% CI, 1.27-1.60; P<0.00001; AA vs. GG+GA: OR, 1.28; 95% CI, 1.16-1.42; P<0.00001). For rs4246215, similar results were identified, as the GG or GT genotype was significantly associated with the increased cancer risk when compared to TT (TT vs. GG: OR, 1.71; 95% CI, 1.52-1.92; P<0.00001; TT vs. GT: OR, 1.34; 95% CI, 1.20-1.50; P<0.00001; TT vs. GG+GT: OR, 1.50; 95% CI, 1.35-1.67; P<0.00001). The present meta-analysis indicated that FEN1 rs174538 and rs4246215 polymorphisms may contribute to an increased risk of cancer.