Promoter Methylation Status of the Retinoic Acid Receptor-Beta 2 Gene in Breast Cancer Patients: A Case Control Study and Systematic Review
Authors: Zohreh Rahimi
Kheirollah Yari
Journal: Breast Care (2019)
Discipline: CLINICAL MEDICINE
Keywords: Breast cancer; Epigenetic; Hypermethylation; Iranian population; MSP

Abstract:  Background: We aimed to determine the promoter methylation status of the retinoic acid receptor-beta 2 (RARβ2) gene among breast cancer patients and to review relevant studies in this field in various populations. Methods: We analyzed 400 samples which comprised blood specimens from 102 breast cancer patients, 102 first-degree female relatives of patients, 100 cancer-free females, 48 breast cancer tissues, and 48 adjacent normal breast tissues from the same patients. The RARβ2 methylation status was determined using methylation-specific polymerase chain reaction (MSP) and DNA sequencing methods. Results: The presence of combined partially methylated (MU) and fully methylated (MM) forms of the RARβ2 gene (MU+MM) in the blood of patients was associated with susceptibility to breast cancer (odds ratio = 4.7, p = 0.05). A significantly higher frequency of the MM genotype was observed in cancer tissue (10.4%) compared to matched adjacent normal breast tissue (0%) (p = 0.02). Conclusion: We found a higher frequency of RARβ2 gene methylation in the blood and cancer tissues of patients compared to the blood of controls and adjacent normal breast tissues. The survey of studies on various populations demonstrated a higher RARβ2 methylation frequency in breast cancer patients compared to normal individuals, and many reports suggest a significant association between hypermethylation of the gene and susceptibility to breast cancer. 

Retracted: No

PubPeer comments:
 Not be afraid if you think something is wrong: Why academic publishing oscillates from its sublime horizon? A letter Dear Editor in Chief, Recently two researchers, Dr. Kheirollah Yari and Prof. Zohreh Rahimi from the Kermanshah University of Medical Science of Iran published a paper in Breast Care journal regarding promoter methylation of the status of RARu03b22 gene in breast cancer patients at which reporting obscure data in this paper keep encouraging on my mind to write this letter. My core contention is that their results spectacularly oscillated from academic publishing standards and my claims directly targeted their outcomes. In this regard, this letter set outs to explain several different errors that may produce further scientific misconduct for relevant studies either by wasting researchersu2019 time or financial sources. I carefully, with a great level of interest, read their paper and the discussed errors in the following lines should be re-investigated emergently, otherwise, the comprehensiveness and entirety of their study cannot be validated or cited in the apropos studies. Errors: This paper suffered from the following errors: 1-The sequence of applied primers for PCR reaction was not reported. 2-The authors reported that their paper dealt with 400 samples of clinical cases while their data doesn t support their claim. I am would like to invite the authors to share their raw materials with the literature. To prove their claims, they should put herein a copy of their agarose gel electrophoresis outputs. 3- The considered sequence in Fig.1 of this study doesn t match with the promoter sequence of the RARu03b22 gene. It quite clear that the authors were not careful about the promoter of this gene well. 4- The authors were mentioned that all participants were entirely agreed with sharing their samples within this study. If they are true, please share the patient s agreements forms herein with validated contacting numbers. It seems their institute, Kermanshah University of Medical Science doesn t approve this study ethically. 5- The title of the paper dealt with the systematic investigation of literature but no systematic criteria at all applied herein. The authors only tabularized some previous studies without considering available standards for performing a systematic review. 6-The conclusion of this paper is not novel or partially different from those studies that reported in table 3. Yari and Rahimi s results formerly reported by other authors several times and the accumulating body of evidence suggests that they don t analyze 400 samples for this work. 7- The reported statistics for tables 1 and 2 seemingly not significant. To best of academic reader knowledge, I would like to ask authors to share their gathered data herein or with an editorial team to re-analyze their statistical model and approach. 8- The authors reported that they sent their sequences for the sequencing process. Please share your sequencing data herein. ab1 format. It is important to the academic readers how much data have sent to be sequenced? 1? 2? 400? 9- The study has not any supplementary data to confirm the fact either the authors performed experimental assays or just fabricated statistical data based upon formerly reported outcomes. 10- Without access to the preliminary data of this study including PCR gel images, raw data, sampling types, ethical agreements and something like that the validation of this paper could not be approved. ,