Expression of BRCA1 mRNA in cancerous and non-cancerous breast tissue of Bangladeshi females attending a tertiary care hospital

Authors

  • Latifa Nishat Department of Anatomy, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh https://orcid.org/0000-0003-1393-6927
  • Sufi Hannan Zulfiqar Rahman Department of Immunology and Molecular Biology, National Institute of Cancer Research and Hospital, Dhaka, Bangladesh https://orcid.org/0000-0001-6202-7004
  • Farida Arjuman Department of Histopathology, National Institute of Cancer Research and Hospital, Dhaka, Bangladesh https://orcid.org/0009-0001-7010-7423
  • Zinnat Ara Yesmin Department of Anatomy, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
  • Lutfun Nahar Department of Anatomy, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh https://orcid.org/0009-0008-8723-7081
  • Umma Habiba Laboni Department of Anatomy, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh https://orcid.org/0009-0009-5110-214X
  • Samira Sultana Amee Department of Anatomy, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
  • Farzana Afroze Department of Anatomy, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh https://orcid.org/0009-0009-5936-5614

DOI:

https://doi.org/10.3329/bsmmuj.v18i1.76754

Keywords:

BRCA1 mRNA expression , breast cancer, fibroadenoma, FFPE cancerous and non-cancerous breast tissue

Abstract

Background: Dysfunctions of the BRCA1 (BReast CAncer gene1) gene are reported in cancerous and non-cancerous breast lesions. BRCA1 mRNA expression is variable in breast cancer, while this information is still inadequate in non-cancerous breast disorders. This study aimed to measure BRCA1 mRNA expression in cancerous and non-cancerous breast tissue of Bangladeshi females.

Methods: The cross-sectional study was conducted on 50 breast cancer and 19 non-cancerous females. RNA was extracted from formalin-fixed paraffin-embedded breast tissue. Real-time RT-PCR was done for measuring BRCA1 mRNA. BRCA1 mRNA expressions in cancerous and non-cancerous breast tissue were compared and analysed.

Results: BRCA1 mRNA expression was reduced or absent in most of the cancerous and non-cancerous (consisting of fibroadenoma, fibrocystic disease, ductal hyperplasia and normal breast tissue) breast tissue. Expression of BRCA1 in breast cancer and fibroadenoma was almost similar statistically. All cancers were invasive ductal carcinoma and of grade II, and most of them were sporadic (86%). BRCA1 expression was not associated with reproductive or cancer-related characteristics except consanguinity of marriage. The non-cancerous females were younger than the cancer patients (33.5 versus 43 years, respectively).

Conclusion: The study suggests the necessity of bringing fibroadenoma patients, in addition to breast cancer patients, into the screening programme and analysing the molecular profile because their BRCA1 expression is similar.

 

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References

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. DOI: https://doi.org/1010.3322/caac.21660

Liede A, Narod SA. Hereditary breast and ovarian cancer in Asia: genetic epidemiology of BRCA1 and BRCA2. Hum Mutat. 2002 Dec;20(6):413-424. DOI: https://doi.org/10.1002/humu.10154

Story HL, Love RR, Salim R, Roberto AJ, Krieger JL, Ginsburg OM. Improving outcomes from breast cancer in a low-income country: lessons from bangladesh. Int J Breast Cancer. 2012;2012:423562. DOI: https://doi.org/10.1155/2012/423562

Turner N, Tutt A, Ashworth A. Hallmarks of 'BRCAness' in sporadic cancers. Nat Rev Cancer. 2004 Oct;4(10):814-819. DOI: https://doi.org/10.1038/nrc1457

Li Q, Wei W, Jiang YI, Yang H, Liu J. Promoter methylation and expression changes of BRCA1 in cancerous tissues of patients with sporadic breast cancer. Oncol Lett. 2015 Apr;9(4):1807-1813. DOI: https://doi.org/10.3892/ol.2015.2908

Leongamornlert D, Mahmud N, Tymrakiewicz M, Saunders E, Dadaev T, Castro E, Goh C, Govindasami K, Guy M, O'Brien L, Sawyer E, Hall A, Wilkinson R, Easton D; UKGPCS Collaborators; Goldgar D, Eeles R, Kote-Jarai Z. Germline BRCA1 mutations increase prostate cancer risk. Br J Cancer. 2012 May 8;106(10):1697-1701. DOI: https://doi.org/ 10.1038/bjc.2012.146

Kim HS, Hwang IG, Min HY, Bang YJ, Kim WH. Clinical significance of BRCA1 and BRCA2 mRNA and protein expression in patients with sporadic gastric cancer. Oncol Lett. 2019 May;17(5):4383-4392. DOI: https://doi.org/10.3892/ol.2019.10132

Amirrad M, Al-Mulla F, Varadharaj G, John B, Saji T, Anim JT. BRCA1 gene expression in breast cancer in Kuwait: correlation with prognostic parameters. Med Princ Pract. 2005 Mar-Apr;14(2):67-72. DOI: https://doi.org/10.1159/000083913

Xu Y, Ouyang T, Li J, Wang T, Fan Z, Fan T, Lin B, Xie Y. Predictive value of BRCA1/2 mRNA expression for response to neoadjuvant chemotherapy in BRCA-negative breast cancers. Cancer Sci. 2018 Jan;109(1):166-173. DOI: https://doi.org/10.1111/cas.13426

Stachs A, Stubert J, Reimer T, Hartmann S. Benign Breast Disease in Women. Dtsch Arztebl Int. 2019 Aug 9;116(33-34):565-574. DOI: https://doi.org/10.3238/arztebl.2019.0565

Zeinomar N, Phillips KA, Daly MB, Milne RL, Dite GS, MacInnis RJ, Liao Y, Kehm RD, Knight JA, Southey MC, Chung WK, Giles GG, McLachlan SA, Friedlander ML, Weideman PC, Glendon G, Nesci S; kConFab Investigators; Andrulis IL, Buys SS, John EM, Hopper JL, Terry MB. Benign breast disease increases breast cancer risk independent of underlying familial risk profile: Findings from a Prospective Family Study Cohort. Int J Cancer. 2019 Jul 15;145(2):370-379. DOI: https://doi.org/10.1002/ijc.32112

Hospital Cancer Registry Report (2018-2020). National Institute of Cancer Research and Hospital, Dhaka. 2022. Accessed on: 6 February 2025. Available from: https://nicrh.gov.bd/reports

Nahar N, Iqbal M, Rahman KMS, Razzaque S, Yeasmin F, Alam U, Uddin MA. Age and Gender Distribution of Benign Breast Lesions of Women at Port City of Bangladesh. J Sci Found. 2018;16(1):27-31. DOI: https://doi.org/10.3329/jsf.v16i1.38176

Egawa C, Miyoshi Y, Taguchi T, Tamaki Y, Noguchi S. Quantitative analysis of BRCA1 and BRCA2 mRNA expression in sporadic breast carcinomas and its relationship with clinicopathological characteristics. Jpn J Cancer Res. 2001 Jun;92(6):624-630. DOI: https://doi.org/10.1111/j.1349-7006.2001.tb01140.x

Wu YT, Chen ST, Chen CJ, Kuo YL, Tseng LM, Chen DR, Kuo SJ, Lai HW. Breast cancer arising within fibroadenoma: collective analysis of case reports in the literature and hints on treatment policy. World J Surg Oncol. 2014 Nov 10;12:335. DOI: https://doi.org/10.1186/1477-7819-12-335

Brunetti N, Valente I, Pitto F, Calabrese M. Triple-negative Breast Cancer Arising in a Fibroadenoma in BRCA 1 Mutated Patient. J Med Ultrasound. 2022 Aug 16;31(1):63-65. DOI: https://doi.org/10.4103/jmu.jmu_83_21

Kuijper A, Preisler-Adams SS, Rahusen FD, Gille JJ, van der Wall E, van Diest PJ. Multiple fibroadenomas harbouring carcinoma in situ in a woman with a family history of breast/ovarian cancer. J Clin Pathol. 2002 Oct;55(10):795-7. DOI: https://doi.org/10.1136/jcp.55.10.795

Chehade R, Pettapiece-Phillips R, Salmena L, Kotlyar M, Jurisica I, Narod SA, Akbari MR, Kotsopoulos J. Reduced BRCA1 transcript levels in freshly isolated blood leukocytes from BRCA1 mutation carriers is mutation specific. Breast Cancer Res. 2016 Aug 17;18(1):87. DOI: https://doi.org/10.1186/s13058-016-0739-8

Xu X, Wagner KU, Larson D, Weaver Z, Li C, Ried T, Hennighausen L, Wynshaw-Boris A, Deng CX. Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation. Nat Genet. 1999 May;22(1):37-43. DOI: https://doi.org/10.1038/8743

Al-Mulla F, Abdulrahman M, Varadharaj G, Akhter N, Anim JT. BRCA1 gene expression in breast cancer: a correlative study between real-time RT-PCR and immunohistochemistry. J Histochem Cytochem. 2005 May;53(5):621-629. DOI: https://doi.org/10.1369/jhc.4A6544.2005

Taylor J, Lymboura M, Pace PE, A'hern RP, Desai AJ, Shousha S, Coombes RC, Ali S. An important role for BRCA1 in breast cancer progression is indicated by its loss in a large proportion of non-familial breast cancers. Int J Cancer. 1998 Aug 21;79(4):334-342. DOI: https://doi.org/10.1002/(sici)1097-0215(19980821)79:4<334::aid-ijc5>3.0.co;2-w

Silva JM, Gonzalez R, Provencio M, Dominguez G, Garcia JM, Gallego I, Palacios J, España P, Bonilla F. Loss of heterozygosity in BRCA1 and BRCA2 markers and high-grade malignancy in breast cancer. Breast Cancer Res Treat. 1999 Jan;53(1):9-17. DOI: https://doi.org/10.1023/a:1006082117266

Baylin SB, Herman JG, Graff JR, Vertino PM, Issa JP. Alterations in DNA methylation: a fundamental aspect of neoplasia. Adv Cancer Res. 1998;72:141-196. PMID: 9338076

Esteller M, Silva JM, Dominguez G, Bonilla F, Matias-Guiu X, Lerma E, Bussaglia E, Prat J, Harkes IC, Repasky EA, Gabrielson E, Schutte M, Baylin SB, Herman JG. Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst. 2000 Apr 5;92(7):564-569. DOI: https://doi.org/10.1093/jnci/92.7.564

Medimegh I, Troudi W, Omrane I, Ayari H, Uhrhummer N, Majoul H, Benayed F, Mezlini A, Bignon YJ, Sibille C, Elgaaied AB. Consanguinity Protecting Effect Against Breast Cancer among Tunisian Women: Analysis of BRCA1 Haplotypes. Asian Pac J Cancer Prev. 2015;16(9):4051-4055. DOI: https://doi.org/10.7314/apjcp.2015.16.9.4051

Grjibovski AM, Magnus P, Stoltenberg C. Decrease in consanguinity among parents of children born in Norway to women of Pakistani origin: a registry-based study. Scand J Public Health. 2009 May;37(3):232-238. DOI: https://doi.org/10.1177/1403494808100939

Denic S, Bener A. Consanguinity decreases risk of breast cancer--cervical cancer unaffected. Br J Cancer. 2001 Nov 30;85(11):1675-1679. DOI: https://doi.org/10.1054/bjoc.2001.2131

Denic S, Frampton C, Nicholls MG. Risk of cancer in an inbred population. Cancer Detect Prev. 2007;31(4):263-269. DOI: https://doi.org/10.1016/j.cdp.2007.07.006

Ludwig T, Chapman DL, Papaioannou VE, Efstratiadis A. Targeted mutations of breast cancer susceptibility gene homologs in mice: lethal phenotypes of Brca1, Brca2, Brca1/Brca2, Brca1/p53, and Brca2/p53 nullizygous embryos. Genes Dev. 1997 May 15;11(10):1226-1241. DOI: https://doi.org/10.1101/gad.11.10.1226

Hohenstein P, Kielman MF, Breukel C, Bennett LM, Wiseman R, Krimpenfort P, Cornelisse C, van Ommen GJ, Devilee P, Fodde R. A targeted mouse Brca1 mutation removing the last BRCT repeat results in apoptosis and embryonic lethality at the headfold stage. Oncogene. 2001 May 3;20(20):2544-50. DOI: https://doi.org/10.1038/sj.onc.1204363

Denic S, Al-Gazali L. Breast cancer, consanguinity, and lethal tumor genes: simulation of BRCA1/2 prevalence over 40 generations. Int J Mol Med. 2002 Dec;10(6):713-719. PMID: 12429997

Nicola M. A positive defect. Nat Rev Cancer. 2005;5(May):333-334. Accessed on: 6 February 2025. Available from: https://doi.org/10.1038/nrc1618

Published

2025-02-13

How to Cite

Nishat, L., Rahman, S. H. Z., Arjuman, F., Yesmin, Z. A., Nahar, L., Laboni, U. H., … Afroze, F. (2025). Expression of BRCA1 mRNA in cancerous and non-cancerous breast tissue of Bangladeshi females attending a tertiary care hospital. Bangabandhu Sheikh Mujib Medical University Journal, 18(1), e76754. https://doi.org/10.3329/bsmmuj.v18i1.76754

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