An updated meta-analysis of association between Tp53 Arg72pro polymorphism and colorectal cancer

Abstract

BACKGROUND: The Tp53Arg72Pro (rs1042522) polymorphism has been reported to be associated with the tumour protein 53 expression and increased colorectal cancer risk. However, studies investigating the association between Tp53 Arg72Pro polymorphism and colorectal cancer risk derived inconsistent outcomes. Therefore, an updated meta-analysis including all current obtainable studies were performed to explore the association of Tp53 Arg72Pro polymorphism with colorectal cancer risk.

METHOD: This meta-analysis was mainly performed based on HuGENet™ Review, a PRISMA-like guideline for conducting meta-analysis on SNPs. A comprehensive search was performed up to April 14, 2015 in MEDLINE (PubMed), ISI Web of Science, EMBASE (Ovid), China National Knowledge Infrastructure (CNKI) and WANFANG. The searching strategy was as follows: (“Tp53” or “p53” or “rs1042522” or “codon 72” or “Arg72Pro”) and (“mutation” or “polymorphism” or “variation”) and (“colorectal cancer” or “colorectal carcinoma” or “colon cancer” or “rectal cancer”). There were no exclusions based on language, time periods, age groups and article types. After data extraction, pooled odds ratio and corresponding 95%CI were computed to measure the strength of association. While stratification analysis and meta-regression were conducted to identify the major sources of heterogeneity, sensitivity analysis were performed to test the robustness of the results and cumulative meta-analysis for chronological consistency testing. In addition, Begg's and Egger's funnel plots were applied to identify the publication bias qualitatively and quantitatively respectively.

RESULTS: 36 eligible observational studies comprising of 9532 colorectal cancer cases and 12556 controls were included in the study. The meta-analysis showed that there were no associations among the whole population (Pro versus Arg: OR=1.08, 95% CI: 0.99-1.17, p=0.08; Arg/Pro versus Arg/Arg: OR = 1.05, 95% CI: 0.95-1.16, p=0.08; Pro/Pro versus Arg/Arg: OR=1.17, 95% CI: 0.99-1.39, p=0.06), but an association in Asians after stratification (Pro versus Arg: OR=1.12, 95% CI: 1.02-1.24, p=0.015; Pro/Pro versus Arg/Arg: OR=1.31, 95% CI: 1.07-1.60, p=0.008). Meta-regression suggests blinded genotyping maybe a major source of heterogeneity, whereas stratification analysis indicates ethnicity plays an important role in the high heterogeneity. No publication bias and small study bias were observed in funnel plot.

CONCLUSION: The study suggests the association between Tp53 codon72polymorphism and colorectal cancer may vary with ethnicities. An association were observed only in Asians in allele-based model and in homozygotes model. The Tp53 Arg72Pro variances might have an implication in the identification of sensitive biomarker of colorectal cancer.