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. 2018 Feb 26;19(2):443-448.
doi: 10.22034/APJCP.2018.19.2.443.

Promoter Methylation of BRCA1, DAPK1 and RASSF1A is Associated with Increased Mortality among Indian Women with Breast Cancer

Prasant Yadav  1   2 , Mirza Masroor, Kajal Nandi, R C M Kaza, S K Jain, Nita Khurana, Alpana Saxena
Affiliations

Promoter Methylation of BRCA1, DAPK1 and RASSF1A is Associated with Increased Mortality among Indian Women with Breast Cancer

Prasant Yadav et al. Asian Pac J Cancer Prev. .

Abstract

Background: Promoter methylation has been observed for several genes in association with cancer development and progression. Hypermethylation mediated-silencing of tumor suppressor genes (TSGs) may contribute to breast cancer pathogenesis. The present study was conducted to investigate the promoter methylation status of BRCA1, DAPK1 and RASSF1A genes in Indian women with breast cancer. Materials and Methods: Promoter methylation was evaluated in DNA extracted from mononuclear cells (MNCs) in peripheral blood samples of 60 histopathologically confirmed newly diagnosed, untreated cases of breast cancer as well as 60 age and sex matched healthy controls using MS-PCR. Association of promoter methylation with breast cancer-specific mortality was analyzed with Cox proportional hazards models. Kaplan-Meier survival analysis was performed for overall survival of the breast cancer patients. Results: We observed a significant increase of BRCA1, DAPK1 and RASSF1A promoter methylation levels by 51.7% (P <0.001), 55.0% (P <0.001) and 46.6% (P <0.001), respectively, when compared to healthy controls. A strong correlation was noted between hypermethylation of the tumor suppressor genes BRCA1 (P= 0.009), DAPK1 (P= 0.008) and RASSF1A (P= 0.02)) with early and advanced stages of breast cancer patients. We also found that breast cancer-specific mortality was significantly associated with promoter methylation of BRCA1 [HR and 95% CI: 3.25 (1.448-7.317)] and DAPK1 [HR and 95% CI: 2.32 (1.05-5.11)], whereas limited significant link was evident with RASSF1A [HR and 95% CI: 1.54 (0.697-3.413]. Conclusion: Our results suggest that promoter methylation of BRCA1, DAPK1 and RASSF1A genes may be associated with disease progression and poor overall survival of Indian women with breast cancer.

Keywords: Promoter methylation; tumor suppressor genes; MS−PCR; breast cancer.

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Figures

Figure 1
Figure 1
Representative Results of MS-PCR Analysis for (A) BRCA1, (B) DAPK1 and (C) RASSF1A in Breast Cancer Patients. Lanes M and U correspond to methylated and unmethylated samples respectively and Last Lane to a 100bp ladder as molecular weight marker.
Figure 2
Figure 2
Kaplan – Meier Survival Plot for Breast Cancer Patients by (a) BRCA1, (b) DAPK1, (c) RASSF1A and (d) BRCA1 + DAPK1 Promoter Methylation Status in Peripheral Blood Samples
See this image and copyright information in PMC

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References

    1. Agathanggelou A, Honorio S, Macartney DP, et al. Methylation associated inactivation of RASSF1A from region 3p21.3 in lung, breast and ovarian tumours. Oncogene. 2001;20:1509–18. - PubMed
    1. Ahmed IA, Pusch CM, Hamed T, et al. Epigenetic alterations by methylation of RASSF1A and DAPK1 promoter sequences in mammary carcinoma detected in extracellular tumor DNA. Cancer Genet Cytogenet. 2010;199:96–100. - PubMed
    1. Bagadi SA, Prasad CP, Kaur AS, et al. Clinical significance of promoter hypermethylation of RASSF1A, RARbeta2, BRCA1 and HOXA5 in breast cancers of Indian patients. Life Sci. 2008;82:1288–92. - PubMed
    1. Baldwin RL, Nemeth E, Tran H, et al. BRCA1 promoter region hypermethylation in ovarian carcinoma:a population-based study. Cancer Res. 2000;60:5329–33. - PubMed
    1. Bean GR, Ibarra Drendall C, et al. Hypermethylation of the breast cancer-associated gene 1 promoter does not predict cytologic atypia or correlate with surrogate end points of breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2007;16:50–6. - PubMed