Three common TP53 polymorphisms in susceptibility to breast cancer, evidence from meta-analysis

The association of polymorphisms of tumor suppressor gene TP53 with breast cancer has widely been reported; however, the results are inconsistent. Here, we selected three commonly studied TP53 polymorphisms: codon 72 Arg > Pro, IVS3 16 bp Del/Ins, and IVS6 + 62A > G to explore their association with breast cancer risk by meta-analysis of published case-control studies. The results showed that codon 72 was not associated with breast cancer risk among 37 combined case-control studies (23,567 cases and 25,995 controls). However, a significant association with decreased risk of breast cancer was found in the Mediterranean studies (PP + PR vs. RR: OR = 0.32, 95% CI = 0.24-0.44, P < 0.001; PP vs. RR: OR = 0.35, 95% CI = 0.21-0.60, P < 0.001). IVS3 16 bp Del/Ins was significantly associated with an increased risk of developing breast cancer in a pooled 8 study dataset (2,470 cases and 2,825 controls; Ins/Ins + Del/Ins vs. Del/Del: OR = 1.15, 95% CI = 1.01-1.30, P = 0.04; Ins/Ins vs. Del/Del: OR = 1.75, 95% CI = 1.20-2.37, P = 0.003). No significant association was observed between IVS6 + 62A > G and breast cancer risk in a total of 10 studies (8,537 cases and 9,586 controls). These results suggest that IVS3 16 bp Del/Ins is likely an important genetic marker contributing to susceptibility of breast cancer, and codon 72 has a potential role in association with breast cancer risk within certain populations or regions.