Association between the p53 codon 72 Arg/Pro polymorphism and hepatocellular carcinoma risk

Previous studies regarding the association of p53 codon 72 Arg/Pro polymorphism with hepatocellular carcinoma (HCC) risk have provided conflicting and inconclusive findings. Thus, a meta-analysis of all currently available publications was performed to address this issue. Eleven individual case–control studies involving a total of 2,718 cases and 3,752 controls were identified after a systematic search of the PubMed, Embase, Web of Science, and Wanfang databases. The strength of the association of p53 codon 72 Arg/Pro polymorphism with HCC risk was estimated by the pooled odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI). Subgroup analyses stratified by ethnicity, source of controls, gender, hepatitis virus infection status, and family history of HCC were also conducted to assess the association. Overall, significantly increased risk of HCC was identified among carriers of the homozygous genotype ProPro (OR_{ProPro vs. ArgArg} = 1.38 (95 % CI, 1.03–1.85), P _OR = 0.033; OR_{ProPro vs. ArgArg + ArgPro} = 1.28 (95 % CI, 1.03–1.59), P _OR = 0.026). In subgroup analysis by ethnicity, the pooled results suggested that the p53 codon 72 Arg/Pro polymorphism was associated with an increased risk of HCC in Asians and Caucasians (for Asians, OR_{ProPro vs. ArgArg + ArgPro} = 1.17 (95 % CI, 1.02–1.34), P _OR = 0.025; for Caucasians, OR_{ProPro vs. ArgArg} = 1.65 (95 % CI, 1.07–2.56), P _OR = 0.025; OR_{ProPro vs. ArgArg + ArgPro} = 1.74 (95 % CI, 1.14–2.66), P _OR = 0.010). Subgroup analyses by source of controls and hepatitis virus infection status further demonstrated the significant association, whereas stratification factors involving gender and family history of HCC did not modify the association between p53 codon 72 Arg/Pro polymorphism and HCC risk. This meta-analysis suggests that the p53 codon 72 Arg/Pro polymorphism may play a critical role in the development of HCC, and gender and family history of HCC may not modulate the effect of p53 codon 72 Arg/Pro in HCC risk.