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G4C14-A4T14 polymorphism of TP73 gene has been reported with a potential association in cancer risks through affected cell homeostasis; however the results were not consistent. We performed a comprehensive meta-analysis to explore the associations between G4C14-A4T14 polymorphism and cancer susceptibility. Extensive retrieve was performed in PubMed, EMBASE, Google Scholar, Web of Science, Wanfang database and CNKI database up to May 20, 2018. Odds ratios (ORs) and 95% confidence intervals (CIs) were conducted to evaluate the overall strength of the associations in five genetic models, as well as in subgroup analyses. Q -test, false-positive report probability analysis and trial sequential analysis, Egger's test and Begg's funnel plot were applied to evaluate the robustness of the results. In silico analysis was managed to demonstrate the relationship of TP73 expression correlated with cancer tissues. Finally, 36 case-control studies with a total of 9493 cancer cases and 13,157 healthy controls were enrolled into the meta-analysis. The pooled results present a significantly higher risk of G4C14-A4T14 polymorphism in all the five genetic models, as well as in the subgroups of Caucasian, cervical cancer, colorectal cancer, H-B subgroup and comfort to Hardy-Weinberg equilibrium subgroup. In silico analysis revealed that the expression of TP73 in cervical cancer tissue is higher than it in corresponding normal tissue, as well as in cervical cancer. All in all, TP73 G4C14-A4T14 polymorphism causes an upgrade cancer risk, especially in Caucasian population. G4C14-A4T14 polymorphism might be a potential biomarker for judging the tumorigenesis of cervical cancer and colorectal cancer.

TP73 G4C14-A4T14polymorphism and cancer susceptibility: evidence from 36 case–control studies