"p53 Polymorphism at Codon 72 and Breast Cancer" - Letter.

Dear Editor:

We read with interest the recently published systematic review and meta-analysis titled “The Evaluation of p53 Polymorphism at Codon 72 and Association With Breast Cancer in Iran: A Systematic Review and Meta-analysis”.1 We believe that there are few important issues in the systematic review and meta-analysis that require clarification. A key characteristic of a systematic review is a comprehensive search to find eligible studies. This study has been conducted between 2007 and 2014, however, one study has been missed.2 According to the date of publication, a study published in 2015 has also been missed.3 Furthermore, Hardy–Weinberg equilibrium (HWE) test is commonly used for quality control of genotyping and is one of the few ways to identify systematic genotyping errors.4 It seems that authors have not considered testing HWE for quality assessment of the included studies. Once we checked, the reported pooled data did not follow the HWE. Therefore, because of the lack of HWE analysis, the interpretation of these results may be difficult.

The appropriate sample size is a major issue in genetic case-control studies analyzing the association of polymorphisms with disease susceptibility. It seems the authors have also missed commenting on the statistical power in this study.

The random-effect method assumingly was used to measure association because of heterogeneity, but identifying the source of the heterogeneity could also be helpful to figure out the properties of those particular studies. Overall, we urge mentioning the missing data and also lack of quality control for the included studies to strengthen the conclusion reached by the authors.