Aberrant methylation of APC and RARβ2 genes in breast cancer patients

Swellam, Menha; Abdelmaksoud, Mohamed D. E.; Mahmoud, Magda Sayed; Ramadan, Amal; Abdel-Moneem, Walid; Hefny, Mohamed

doi:10.1002/iub.1346

Cited by 37 publications

(22 citation statements)

References 18 publications

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“…Studies by Zmetakova I et al and Brooks JD et al reported no significant differences in methylation of APC between cases and controls.Zmetakova I, 2013 [42]PlasmaPyrosequencing (mean ± SD)34/5041–90/20–784.41 ± 7.812.53 ± 1.560.06Radpour R, 2011 [47]PlasmaEpiTyper assay (mean)36/3067/na0.39 b 0.19 b <0.0001Brooks JD, 2010 [56] d SerumQMSP (%)49/9652/51.824.2>0.05Hoque M, 2006 [44]PlasmaQMSP (%)47/3844.9/37.31700.008Van der Auwera I, 2009 [52]SerumQMSP (%)79/1962/392950.03Dulaimi E, 2004 [50]SerumMSP (%)34/2057.4/57.4290<0.05 c ESR1 Zmetakova I, 2013 [42]PlasmaPyrosequencing (mean ± SD)34/5041–90/20–784.18 ± 4.075.24 ± 4.330.338Only one study (Matinez-Galan, J) reported higher methylation levels of ESR1 in BC patients. Others observed no significant methylation differences.Zurita M, 2010 [54]SerumQMSP (%)77/34na/na0.005 b 0.085 b >0.05Van der Auwera I, 2009 [52]SerumQMSP (%)79/1962/392010.50.33Martinez-Galan J, 2008 [51]SerumMSP (%)106/7458/420.11 b 0.02 b 0.011 RARB Swellam M, 2015 [59]SerumMS-PCR (%)121/6643/4095.90<0.0001Higher frequency of methylated RARB was observed except the study conducted by Brooks JD et alBrooks JD, 2010 [56…”

Section: Resultsmentioning

confidence: 99%

“…With ten studies, RASSF1A was the most frequently evaluated gene and eight of them reported higher frequency of methylated RASSF1A in BC patients compared to controls [42, 44–46, 50, 52, 55–58]. APC has been investigated in seven studies [42, 44, 47, 50, 52, 56, 59]. Among them, five studies reported higher frequency of methylated APC in plasma/serum DNA of BC patients.…”

Section: Resultsmentioning

confidence: 99%

“…Among them, five studies reported higher frequency of methylated APC in plasma/serum DNA of BC patients. Higher frequency of methylated RARB (also known as RARβ2 ) was observed in four studies [44, 56, 57, 59]. Methylation levels of ESR1 [42, 51, 52, 54], GSTP1 [44, 47, 56], and TIMP3 [42, 47] were each investigated in two or more studies, but each gene yielded with inconclusive results.…”

Section: Resultsmentioning

confidence: 99%

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Blood-based DNA methylation as biomarker for breast cancer: a systematic review

et al. 2016

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Multiple studies have investigated global DNA methylation profiles and gene-specific DNA methylation in blood-based DNA to develop powerful screening markers for cancer. This systematic review summarizes the current evidence on methylation studies that investigated methylation level of blood-derived DNA of breast cancer (BC) patients in comparison to healthy controls by conducting a systematic literature review in PubMed and Web of Science. Essential results, such as methylation levels of BC cases and healthy controls, p values, and odds ratios, were extracted from these studies by two investigators independently. Overall, 45 publications met the inclusion criteria for this review. DNA from whole blood, as well as cell-free DNA (cfDNA) from serum or plasma, was used in these studies. The most common method used for measuring global DNA methylation was the investigation of repetitive elements as surrogates and the application of array-based genome-wide methylation analysis. For measuring gene-specific methylation level, methylation-specific PCR and pyrosequencing were the most frequently used methods. Epigenome-wide blood DNA hypomethylation in BC patients were reported in several studies; however, the evidence is still not conclusive. The most frequently investigated gene in whole blood was BRCA1, which was found more frequently methylated in patients compared to controls. RASSF1A was the most widely investigated gene in cfDNA of serum or plasma, which was also found more frequently methylated in patients compared to controls. Several of the eligible studies reported the associations of global hypomethylation and increased BC risk. Studies investigated associations between gene-specific methylation and BC risk, while got heterogeneous results. But two studies reported that hypermethylation of ATM gene was associated with increased BC risk, which suggest the potential use of this gene for BC risk stratification. Overall, our review suggests the possibility of using blood-based DNA methylation marker as promising marker for BC risk stratification, as several studies found associations between certain methylation level in blood and BC risk. However, so far, the evidence is still quite limited. Optimal markers are yet to be developed and promising results needed to be validated in prospective study cohorts and tested in large screening populations.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0282-6) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Blood-based DNA methylation as biomarker for breast cancer: a systematic review

et al. 2016

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“…Among 29 studies, there were 26 case-control studies [12, 14, 15–33, 35, 37–40] and 3 cohort studies [35, 36, 41]. Interestingly, 12 studies [12, 14, 15, 18, 19, 22, 24, 26–28, 32, 38] among 26 case-control studies also did the cohort analyses.…”

Section: Resultsmentioning

confidence: 99%

Quantitative assessment of the association between APC promoter methylation and breast cancer

Zhang

Long

2016

Oncotarget

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Adenomatous polyposis coli (APC) is an important tumor suppressor gene in breast cancer. However, there were inconsistent conclusions in the association between APC promoter methylation and breast cancer. Hence, we conducted a meta-analysis to quantitatively assess the clinicopathological significance and diagnosis role of APC methylation in breast cancer. In total, 3172 samples from 29 studies were performed in this study. The odds ratio (OR) of APC methylation was 5.92 (95% CI = 3.16–11.07) in breast cancer cases compared to controls,. The APC promoter methylation was associated with cancer stage (OR = 0.47, 95% CI = 0.28–0.80, P = 0.006), lymph node metastases (OR = 0.55, 95% CI = 0.36–0.84, P = 0.005) and ER status (OR = 1.34, 95% CI = 1.03–1.73, P = 0.003) in breast cancer. Furthermore, the sensitivity and specificity for all included studies were 0.444 (95% CI: 0.321–0.575, P < 0.0001) and 0.976 (95% CI: 0.916–0.993, P < 0.0001), respectively. These results suggested that APC promoter methylation was associated with breast cancer risk, and it could be a valuable biomarker for diagnosis, treatment and prognosis of breast cancer.

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“…Hence, the results obtained in our study could be confirmed using a quantitative MSP method. However, a number of studies have suggested that MSP has a high sensitivity and specificity for the identification of breast cancer cells [21,22]. A frequency of 10-42% for the methylation of RARβ2 in the promoter region of breast cancer tissue has been reported [23].…”

Section: Discussionmentioning

confidence: 99%

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

Yari¹,

Rahimi

2019

Breast Care

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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.

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Aberrant methylation of APC and RARβ₂ genes in breast cancer patients

Cited by 37 publications

References 18 publications

Blood-based DNA methylation as biomarker for breast cancer: a systematic review

Blood-based DNA methylation as biomarker for breast cancer: a systematic review

Quantitative assessment of the association between APC promoter methylation and breast cancer

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

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