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. 2019 Apr;14(2):117-123.
doi: 10.1159/000489874. Epub 2019 Jan 30.

Promoter Methylation Status of the Retinoic Acid Receptor-Beta 2 Gene in Breast Cancer Patients: A Case Control Study and Systematic Review

Kheirollah Yari  1 , Zohreh Rahimi  1   2
Affiliations

Promoter Methylation Status of the Retinoic Acid Receptor-Beta 2 Gene in Breast Cancer Patients: A Case Control Study and Systematic Review

Kheirollah Yari et al. Breast Care (Basel). 2019 Apr.

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.

Keywords: Breast cancer; Epigenetic; Hypermethylation; Iranian population; MSP; RARβ2.

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Conflict of interest statement

The authors declare no potential or actual conflicts of interest in relation to the current article.

Figures

Fig. 1
Fig. 1
Analysis of a fragment of the RARβ2 gene in the promoter region using a DNA sequencing apparatus (Macrogen Inc., Seoul, South Korea). A Promoter sequence of the RARβ2 gene in the NCBI database; B obtained sequences from MethPrimer software; C sequences obtained by DNA sequencing using a sodium bisulfite-treated sample. Underlined CG represents the CpG islands that have not been modified by sodium bisulfite treatment and remained intact as CG, whereas those C* nucleotides that were not followed by a G nucleotide were modified to T after sodium bisulfite modification (B).
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