Role of Estrogen Receptor Alpha rs3798577 Polymorphism in Breast Carcinoma Risk Determination

Pieri Kumaladewi, Wirsma Arif Harahap, Bastian Nova, Irianiwati Widodo, Ramadhan Karsono, Ferry Sandra, Bethy Suryawathy Hernowo


BACKGROUND: Interaction between estrogen and estrogen receptor (ER) takes part in the regulation and differentiation of breast tumorigenesis. Some ERα polymorphisms, including ERα rs3798577, are reported to be associated with the risk and aggressiveness of breast carcinoma since the site was reported to be targeted by microRNA, which can further modulate the ERα expression. Hence, this study was conducted to disclose the possible role of ERα SNP rs3798577 on breast carcinoma patients.

METHODS: Samples were taken from the post-mastectomy breast carcinoma tissues of female patients and screened based on the completeness of medical and histopathological records. DNA isolation was proceeded using real time-polymerase chain reaction (RT-PCR) then analyzed for high resolution melting (HRM). The nucleotide base sequence was then analyzed based on rs3798577 ERα polymorphism. ER immunohistochemistry test was carried out and counted quantitatively based on the staining intensity and the percentage of the stained cells.

RESULTS: Out of 65 samples, there were 33 samples as wild type and 32 samples as variant type. Most variant and wild type had >80% ERα percentage. Most variant type had middle ERα intensity, while wild type had strong ERα intensity. Higher percentage of variant type (52.2%) was found with weak ERα histoscore, meanwhile higher percentage of wild type (52.4%) was found with strong ERα histoscore, but not significant (p=0.725).

CONCLUSION: ERα rs3798577 variant type had a lower ERα intensity and weaker ERα histoscore compared to the wild type, suggesting that ERα rs3798577 polymorphism might play a role in breast carcinoma risk determination.

KEYWORDS: breast cancer, ERα, rs3798577, polymorphism, immunoexpression

Full Text:



Savitri M, Bintoro UY, Sedana MP, Diansyah MN, Romadhon PZ, Amrita PNA, et al. Circulating plasma miRNA-21 as a superior biomarker compared to CA 15-3: assessment in healthy age matched subjects and different stage of breast cancer patients. Indones Biomed J. 2020; 12(2): 157-64, CrossRef.

Widowati W, Jasaputra DK, Sumitro SB, Widodo MA, Afifah E, Rizal E, et al. Direct and indirect effect of TNFa and IFNg toward apoptosis in breast cancer cells. Mol Cell Biomed Sci. 2018; 2(2): 60-9, CrossRef.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6): 394-424, CrossRef.

Lei Shaoyuan, Zheng R, Zhang S, Wang S, Chen R, Sun K, et al. Global patterns of breast cancer incidence and mortality A population‐based cancer registry data analysis from 2000 to 2020. Cancer Commun (Lond). 2021; 41(11): 1183-94, CrossRef.

Kimman M, Norman R, Jan S, Kingston D, Woodward M. The burden of cancer in member countries of the association of southeast asian nations (ASEAN). Asian Pacific J Cancer Prev. 2012; 13(2): 411-20, CrossRef.

Indonesian Ministry of Health. Data and health information of cancer situation. In: IGARSS 2014 at Quebec City, QC, Canada, July 13-18, 2014. Canada: IEEE; 2015. p.1-5.

Ilyan T, Retnoningrum D, Hendrianingtyas M, Widyaningrum D, Rachmawati B. Association of 25-hydroxyvitamin D, cyclooxygenase-2 and prostaglandin E2 serum levels in breast cancer patients. Indones Biomed J. 2021; 13(4): 426-32, CrossRef.

Rayter Z. Steroid receptors in breast cancer. Br J Surg. 1991; 78(5): 528-35, CrossRef.

Sommer S, Fuqua SAW. Estrogen receptor and breast cancer. Semin Cancer Biol. 2001; 11(5): 339-52, CrossRef.

Yaşar P, Ayaz G, User SD, Güpür G, Muyan M. Molecular mechanism of estrogen–estrogen receptor signaling. Reprod Med Biol. 2017; 16(1): 4-20, CrossRef.

Fuentes N, Silveyra P. Estrogen receptor signaling mechanisms. Adv Protein Chem Struct Biol. 2019; 116(March): 135-70, CrossRef.

Carausu M, Bidard FC, Callens C, Melaabi S, Jeannot E, Pierga JY, et al. ESR1 mutations: a new biomarker in breast cancer. Expert Rev Mol Diagn. 2019; 19(7): 599-611, CrossRef.

Ali S, Coombes RC. Estrogen receptor alpha in human breast cancer: occurrence and significance. J Mammary Gland Biol Neoplasia. 2000; 5(3): 271-81, CrossRef.

Reinert T, Saad ED, Barrios CH, Bines J. Clinical implications of ESR1 mutations in hormone receptor-positive advanced breast cancer. Front Oncol. 2017; 7(March): 1-9, CrossRef.

Widodo I, Dwianingsih EK, Aryandono T, Soeripto. Clinicopathological characteristic and prognostic significance of indonesian triple negative breast cancer. Indones Biomed J. 2019; 11(3): 286-92, CrossRef.

Purwanto I, Heriyanto DS, Ghozali A, Widodo I, Dwiprahasto I, Aryandono T, et al. Basal-like subgroup is associated with younger age, increased expression of androgen receptor, and worse prognosis, while non-basal-like subtype is associated with higher BMI in triple-negative breast cancer patients. Indones Biomed J. 2020; 12(4): 349-54, CrossRef.

Wang Y, Waters J, Leung ML, Unruh A, Roh W, Shi X, et al. Clonal evolution in breast cancer revealed by single nucleus genome sequencing. PMC. 2014; 512(7513): 155-60, CrossRef.

Son BH, Kim MK, Yun YM, Kim HJ, Yu JH, Ko BS, et al. Genetic polymorphism of ESR1 rs2881766 increases breast cancer risk in Korean women. J Cancer Res Clin Oncol, CrossRef.

Lipphardt MF, Deryal M, Ong MF, Schmidt W, Mahlknecht U. ESR1 single nucleotide polymorphisms predict breast cancer susceptibility in the central European Caucasian population. Int J Clin Exp. 2013; 6(4): 282-8, PMID.

Ripperger T, Gadzicki D, Meindl A, Schlegelberger B. Breast cancer susceptibility: Current knowledge and implications for genetic counselling. Eur J Hum Genet. 2009; 17(6): 722-31, CrossRef.

Anghel A, Raica M, Narita D, Seclaman E, Nicola T, Ursoniu S, et al. Estrogen receptor alpha polymorphisms: correlation with clinicopathological parameters in breast cancer. Neoplasma. 2010; 57(4): 306-15, CrossRef.

Li T, Zhao J, Yang J, Ma X, Dai Q, Huang H, et al. A meta-analysis of the association between ESR1 genetic variants and the risk of breast cancer. PLoS One. 2016; 11(4): e0153314, CrossRef.

Tapper W, Hammond V, Gerty S, Ennis S, Simmonds P, Collins A, et al. The influence of genetic variation in 30 selected genes on the clinical characteristics of early onset breast cancer. Breast Cancer Res. 2008; 10(6): 1-10, CrossRef.

Ireka Y, Agustina H, Aziz A, Hernowo BS, Suryanti S. Comparison of fixation methods for preservation cytology specimens of cell block preparation using 10% neutral buffer formalin and 96% alcohol fixation in E-cadherin and Ki-67 immunohistochemical examination. Open Access Maced J Med Sci. 2019; 7(19): 3139-44, CrossRef.

Jansen RP. mRNA localization: Message on the move. Nat Rev Mol Cell Biol. 2001; 2(4): 247-56, CrossRef.

Bashirullah A, Cooperstock RL, Lipshitz HD, Lipshitz H. Spatial and temporal control of RNA stability. Proc Natl Acad Sci USA. 2001; 98(13): 7025-8, CrossRef.

Jeon T, Kim A, Kim C. Automated immunohistochemical assessment ability to evaluate estrogen and progesterone receptor status compared with quantitative reverse transcription-polymerase chain reaction in breast carcinoma patients. J Pathol Transl Med. 2021; 55(1): 33-42, CrossRef.

Ma H, Lu Y, Marchbanks PA, Folger SG, Strom BL, McDonald JA, et al. Quantitative measures of estrogen receptor expression in relation to breast cancer-specific mortality risk among white women and black women. Breast Cancer Res. 2013; 15(5): R90, CrossRef.

Ghali RM, Al-Mutawa MA, Al-Ansari AK, Zaied S, Bhiri H, Mahjoub T, et al. Differential association of ESR1 and ESR2 gene variants with the risk of breast cancer and associated features: A case-control study. Gene. 2018; 651: 194-9, CrossRef.

van der Ploeg P, van Lieshout LAM, van de Stolpe A, Bosch SL, Lentjes-Beer MHFM, Bekkers RLM, et al. Functional estrogen receptor signaling pathway activity in high-grade serous ovarian carcinoma as compared to estrogen receptor protein expression by immunohistochemistry. Cell Oncol. 2021; 44(4): 951-7, CrossRef.

Ross DS, Zehir A, Brogi E, Konno F, Krystel-Whittemore M, Edelweiss M, et al. Immunohistochemical analysis of estrogen receptor in breast cancer with ESR1 mutations detected by hybrid capture-based next-generation sequencing. Mod Pathol. 2019; 32(1): 81-7, CrossRef.

Al-Eitan LN, Rababa'h DM, Alghamdi MA, Khasawneh RH. Association between ESR1, ESR2, HER2, UGT1A4, and UGT2B7 polymorphisms and breast Cancer in Jordan: a case-control study. BMC Cancer. 2019; 19(1): 1257, CrossRef.

Nyante SJ, Gammon MD, Kaufman JS, Bensen JT, Lin DY, Barnholtz-Sloan JS, et al. Genetic variation in estrogen and progesterone pathway genes and breast cancer risk: an exploration of tumor subtype-specific effects. Cancer Causes Control. 2015; 26(1): 121-31, CrossRef.

Li N, Dong J, Hu Z, Shen H, Dai M. Potentially functional polymorphisms in ESR1 and breast cancer risk: a meta-analysis. Breast Cancer Res Treat. 2010; 121(1): 177-84, CrossRef.

Ahearn TU, Zhang H, Michailidou K, Milne RL, Bolla MK, Dennis J, et al. Common variants in breast cancer risk loci predispose to distinct tumor subtypes. Breast Cancer Res. 2022; 24(1): 2, CrossRef.

Damodaran S, Hortobagyi GN. Estrogen receptor: a paradigm for targeted therapy. Cancer Res. 2021; 81(21): 5396-8, CrossRef.

Rozeboom B, Dey N, De P. ER+ metastatic breast cancer: past, present, and a prescription for an apoptosis-targeted future. Am J Cancer Res. 2019; 9(12): 2821-31, PMID.


Copyright (c) 2022 The Prodia Education and Research Institute

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.


Indexed by:






The Prodia Education and Research Institute