Meta-analysis, The Tp53 Arg72pro Single Nucleotide Polymorphisms And Lung Cancer Susceptibility

The TP53 tumor suppressor gene is involved in a multiple cellular processes. Once the TP53 protein is activated, it can trigger the expression of several genes that influence cell cycle arrest and DNA repair or lead to apoptosis when DNA repair is failed. Located in TP53 exon 4 at Arg/Pro, there is a single nucleod polymorphism (SNP) which results in a nonsynonymous amino acid substitution of an arginine with a proline. Due to the central role of TP53 in the development of tumors and the different function between the Arg and the Pro allele, a great many of studies have investigated the association between this polymorphism and the risk of lung cancer. However, the conclusion is still inconsistent.To evaluate the relationship between TP53 Arg/Pro polymorphism and lung cancer, we performed a Meta-analysis for relevant articles from literature searche, including subgroup analysis, sensitivity analysis, heterogeneity test and publication bias investigation. On one hand, Meta-analysis can effectively improve the statistical power and give a more conclusive conclusion; on the other hand, Meta-analysis is a powerful tool to explore the sources of heterogeneity between studies and can guide the design and interpretation of genetic association studies.Compared with earlier meta-analysis about TP53 Arg/Pro polymorphism in lung cancer, our analysis used more criteria to identify eligible articles and included larger population. Based on the search criteria and inclusion criteria, a total of 9387 lung cancer patients and 9922 cancer-free controls were available from 24 articles (26 studies).In the subgroup analysis stratified by population, there was no statistical association between Pro allele and lung cancer risk in Caucasians compared to allele Arg. However, the association was observed in all subjects, as well as in Asians. The association was also found in Asians under recessive genetic model and homozygote comparison (CC vs. GG). In the subgroup analysis stratified by cancer type,12139C allele might increase the lung adenocarcinoma risk compared to 12139G allele, and the effect was also found under recessive genetic model and homozygote comparison. In the subgroup analysis stratified by cancer stage, there was an elevated association between the 12139C and the stage I lung cancer under dominant genetic model, but no association was observed in other stages. In the subgroup analysis stratified by smoking status, no association of smoking was found between 12139C allele and lung cancer under different genetic models. Sensitivity analysis showed that the relationship between TP53 Arg/Pro polymorphism and the risk of lung cancer was not influenced by single study in Asian population. However, the heterogeneity was observed in overall population and Caucacian population which may reduce reliability of the association. More studies should be performed to clarify the role of TP53 Arg/Pro polymorphism in the development of lung cancer.