Clinical significance of promoter hypermethylation of RASSF1A, RARβ2, BRCA1 and HOXA5 in breast cancers of Indian patients

Bagadi, Sarangadhara Appala Raju; Prasad, Chandra Prakash; Kaur, Jasbir; Srivastava, Anurag; Prashad, Rajinder; Gupta, Sanchita; Ralhan, Ranju

doi:10.1016/j.lfs.2008.04.020

Cited by 22 publications

(25 citation statements)

References 35 publications

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“…Among our studied population, the frequency of methylated RARβ2 was found to be 18.8% in cancer tissues, which is lower than that reported for the population of Tehran (36.4%), the capital and a cosmopolitan city of Iran [24]. However, similarity between the frequency of RARβ2 methylation in breast cancer tissue in the present study (18.8%) and some Asian countries such as India (15%) [25] could be attributed to genetic admixture since the Kermanshah province is historically known as the gate of Asia through which passed the important silk road [26]. Also, the type of examined sample (blood or tissue) could be a reason for discrepancy in the reported methylation rates of RARβ2 among various populations.…”

Section: Discussioncontrasting

confidence: 65%

“…In many populations, including American [27,28,29,30], Chinese [31], Indian [25], Portuguese [32], and Belgian [33], a significant association between the methylation status of the RARβ2 gene and breast cancer incidence has been observed. Further, a meta-analysis by Fang et al [34] reported that the methylation rate of RARβ2 is significantly increased among breast cancer patients compared to cancer-free controls.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussioncontrasting

confidence: 65%

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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“…Heterogeneity is observed both with respect to frequency and clinical correlations. The reported frequency of BRCA1 promoter hypermethylation in sporadic breast carcinomas is in the range of 9 to 59% (15,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). The frequency found here is the first reported in Bulgarian patients with BC and is a little below the average BRCA1 hypermethylation frequency.…”

Section: Discussionmentioning

confidence: 43%

“…Thus, though not a rule, most studies demonstrated that BRCA1 hypermethylation correlated with lack of estrogen and progesterone receptor expression (19,20,22,24,25,30) and is most frequently present in younger women, below the age of 50 (19,24,29). As this in some way resembles the familial BRCA1 mutated tumors, it has been suggested that BRCA1 hypermethylated tumors might phenocopy familial BRCA1 tumors (31).…”

Section: Discussionmentioning

confidence: 99%

Breast cancer patients with hypermethylation in the promoter of BRCA1 gene exhibit favorable clinical status

Krasteva¹,

Bozhanov²,

G³

et al. 2012

neo

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Promoter hypermethylation was shown to be involved in human cancerogenesis through silencing gene expression. Several studies were dedicated to explore the frequency and clinical significance of BRCA1 hypermethylation in sporadic breast cancer to identify a specific molecular and clinico-pathological phenotype. However the available data are limited and rather too heterogeneous. In this study we investigated the level of methylation in the promoter region of BRCA1 and its correlation with clinico-pathological and molecular characteristics in a group of 135 Bulgarian patients. Methylation specific PCR was applied to determine methylation status of tumor samples. Clinical impact of BRCA1 hypermethylation was estimated using standard statistical methods including Fisher's exact and the Chi-squared tests, the Kaplan-Meier method, the univariate and multivariate Cox proportional hazards regression model. We found that hypermethylation was present in 17.04% of the cases (23/135). Patients with hypermethylation in BRCA1 displayed favorable clinical status as their tumors were smaller in size (P = 0.066), lacked p53 gene mutations (P = 0.073) and were of lobular type (P = 0.046). The presence of hypermethylation was weakly associated with better overall survival (P = 0.2) with a hazard ratio of 0.47 (95% CI 0.14-1.54, P = 0.213). Our study provides the first data on the BRCA1 hypermethylation of Bulgarian patients and contributes to elucidation of its clinical significance in sporadic breast cancer. Key words: Breast cancer, BRCA1, Hypermethylation, Clinicopathological characteristics, Overall survivalBreast cancer (BC) represents a major challenge to modern human oncology because of its high and constantly increasing frequency, and growing mortality and morbidity rate in women below the age of 45. Every year in Bulgaria, approximately 3600 women are diagnosed and about 1300 die of BC (1). The major risk factors are sex, age, family predisposition, as well as some reproductive and hormonal factors like early menarche and late menopause, late first childbirth, shorter breastfeeding period, use of oral contraceptives and hormone replacement therapy. Clinically BC is very heterogeneous, which is due to heterogeneity in disease mechanisms.BC results from accumulation of genetic and epigenetic changes in tumor suppressor genes and proto-oncogenes. Some of these genes -р53, PIK3CA, CHEK2, АТМ, HER2, are involved in the pathogenesis of different type of tumors. Others are specific only to breast/ovarian cancer -BRCA1 and BRCA2. A large number of studies demonstrate a correlation between the genetic/epigenetic status of BC related genes and clinicopathological characteristics of the patients. Such investigations could contribute to a more effective BC prevention and therapy, which will increase the survival rate and will significantly improve the quality of life of the patients. However, the results so far are contradictory and need further elucidation.BRCA1 (BReast CAncer susceptibility gene 1) tumor suppressor gene maps to 17...

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“…When we reviewed the literature, the methylation frequency of RAR 2 varied also widely and was ranged from 10 to 41% (Shukla et al 2006;Li et al 2006;Yang et al 2001). Our data showed that RAR 2 was methylated in 70% (56/80) of cases; this frequency is higher in comparison with other studies on Caucasians, Koreans, or Indians (Lee et al 2007;Bagadi et al 2008). However, the frequencies of promoter methylation for CDH1 and p16 INK4a were within the range reported in previous studies of breast cancer (Nass et al 2000;Herman et al 1996;Lehmann et al 2002;Sharma et al 2007;DuVy 2006).…”

Section: Discussionmentioning

confidence: 47%

Aberrant methylation of RASSF1A is associated with poor survival in Tunisian breast cancer patients

Karray-Chouayekh

Trifa

Khabir

et al. 2009

J Cancer Res Clin Oncol

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Clinical significance of promoter hypermethylation of RASSF1A, RARβ2, BRCA1 and HOXA5 in breast cancers of Indian patients

Cited by 22 publications

References 35 publications

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

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

Breast cancer patients with hypermethylation in the promoter of BRCA1 gene exhibit favorable clinical status

Aberrant methylation of RASSF1A is associated with poor survival in Tunisian breast cancer patients

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