Prevalence and Clinical Implications of BRCA1 and BRCA2 Mutations in Breast and Ovarian Cancer Among Pakistani Women

Tahrim Zafar; Zeeshan  Asghar; Urooj  Liaqat; Saira Zafar; Areeba Khan; Muqadas  Naseer

doi:10.62497/IRABCS.83

Authors

Tahrim Zafar University of Sialkot, Sialkot, Pakistan Author https://orcid.org/0009-0009-7317-8575
Zeeshan Asghar University of Sialkot, Sialkot, Pakistan Author
Urooj Liaqat University of Sialkot, Sialkot, Pakistan Author
Saira Zafar Islam Medical and Dental College Sialkot, Sialkot, Pakistan Author
Areeba Khan University of Sialkot, Sialkot, Pakistan Author
Muqadas Naseer Imran Idrees Institute of Rehabilitation Sciences, Sialkot, Pakistan Author

DOI:

https://doi.org/10.62497/IRABCS.83

Keywords:

BRCA1, BRCA2, breast cancer, ovarian cancer, genetic mutations, Pakistan, tumor subtypes, hereditary cancer

Abstract

Background: Major causes of hereditary breast and ovarian cancers are mutations in the BRCA1 and BRCA2 genes, especially affecting cancer type, onset, and prognosis.

Objective: To investigate the frequency and clinical correlations of BRCA1 and BRCA2 mutations among breast and ovarian cancer patients, as well as individuals with strong family histories, in a Pakistani population.

Methodology: This observational cross-sectional study was conducted in the Department of Medical Laboratory Technology at the University of Sialkot. Using a practical sampling technique, 168 female participants—including those with a substantial family history and diagnosed breast and ovarian cancer sufferers—were gathered. Blood or tissue samples were first stripped of DNA, then subjected to PCR and sequencing to identify BRCA1 and BRCA2 mutations. SPSS version 25 was used to analyze data; significance was defined at p <0.05.

Results: Among breast cancer patients, 17.65% had BRCA1 and 11.76% had BRCA2 mutations. In ovarian cancer patients (n=43), 25.58% had BRCA1 and 18.60% had BRCA2 mutations. BRCA1 mutations were more frequent in younger age groups (25.00% in 18–30 years), and were significantly associated with triple-negative tumors (53.13%). BRCA2 mutations were more often found in hormone receptor-positive tumors (50.00%). A strong family history of breast cancer was observed in over 60% of BRCA mutation carriers.

Conclusion: BRCA1 and BRCA2 mutations are prevalent in Pakistani breast and ovarian cancer patients and are closely linked to age at diagnosis, tumor subtype, and family history.

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Author Biographies

Tahrim Zafar, University of Sialkot, Sialkot, Pakistan

Department of MLT
Zeeshan Asghar , University of Sialkot, Sialkot, Pakistan

Department of MLT
Urooj Liaqat , University of Sialkot, Sialkot, Pakistan

Department of MLT
Saira Zafar, Islam Medical and Dental College Sialkot, Sialkot, Pakistan

BS MLT
Areeba Khan, University of Sialkot, Sialkot, Pakistan

Department of MLT
Muqadas Naseer, Imran Idrees Institute of Rehabilitation Sciences, Sialkot, Pakistan

Department of MLT

References

Stewart C, Ralyea C, Lockwood S. Ovarian cancer: an integrated review. InSeminars in oncology nursing 2019 Apr 1 (Vol. 35, No. 2, pp. 151-156). WB Saunders. https://doi.org/10.1016/j.soncn.2019.02.001.

Irigaray P, Newby JA, Clapp R, Hardell L, Howard V, Montagnier L, Epstein S, Belpomme D. Lifestyle-related factors and environmental agents causing cancer: an overview. Biomedicine & pharmacotherapy. 2007 Dec 1;61(10):640-58. https://doi.org/10.1016/j.biopha.2007.10.006.

Welcsh PL, King MC. BRCA1 and BRCA2 and the genetics of breast and ovarian cancer. Human molecular genetics. 2001 Apr 1;10(7):705-13. https://doi.org/10.1093/hmg/10.7.705.

Shivji MK, Venkitaraman AR. DNA recombination, chromosomal stability and carcinogenesis: insights into the role of BRCA2. DNA repair. 2004 Aug 1;3(8-9):835-43. https://doi.org/10.1016/j.dnarep.2004.03.008.

Venkitaraman AR. How do mutations affecting the breast cancer genes BRCA1 and BRCA2 cause cancer susceptibility?. DNA repair. 2019 Sep 1;81:102668. https://doi.org/10.1016/j.dnarep.2019.102668.

Miklikova S, Trnkova L, Plava J, Bohac M, Kuniakova M, Cihova M. The role of BRCA1/2-mutated tumor microenvironment in breast cancer. Cancers. 2021 Feb 2;13(3):575. https://doi.org/10.3390/cancers13030575

Orr KS, Savage KI. The BRCA1 and BRCA2 breast and ovarian cancer susceptibility genes—implications for DNA damage response, DNA repair and cancer therapy. InAdvances in DNA Repair 2015 Nov 18 (pp. 217-253). Intech. DOI: 10.5772/59996

Pourmasoumi P, Moradi A, Bayat M. BRCA1/2 mutations and breast/Ovarian cancer risk: a new insights review. Reproductive Sciences. 2024 Aug 6:1-1. https://doi.org/10.1007/s43032-024-01666-w.

Meyerson M, Gabriel S, Getz G. Advances in understanding cancer genomes through second-generation sequencing. Nature Reviews Genetics. 2010 Oct;11(10):685-96. https://doi.org/10.1038/nrg2841

Bertram JS. The molecular biology of cancer. Molecular aspects of medicine. 2000 Dec 1;21(6):167-223. https://doi.org/10.1016/S0098-2997(00)00007-8

Dziadkowiec KN, Gąsiorowska E, Nowak-Markwitz E, Jankowska A. PARP inhibitors: review of mechanisms of action and BRCA1/2 mutation targeting. Menopause Review/Przegląd Menopauzalny. 2016 Dec 1;15(4):215-9. https://doi.org/10.5114/pm.2016.65667.

Copson ER, Maishman TC, Tapper WJ, Cutress RI, Greville-Heygate S, Altman DG, Eccles B, Gerty S, Durcan LT, Jones L, Evans DG. Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study. The lancet oncology. 2018 Feb 1;19(2):169-80. /dx.doi.org/10.1016/ S1470-2045(17)30891-4

Greenup R, Buchanan A, Lorizio W, Rhoads K, Chan S, Leedom T, King R, McLennan J, Crawford B, Kelly Marcom P, Shelley Hwang E. Prevalence of BRCA mutations among women with triple-negative breast cancer (TNBC) in a genetic counseling cohort. Annals of surgical oncology. 2013 Oct;20:3254-8. https://doi.org/10.1245/s10434-013-3205-1

Fackenthal JD, Olopade OI. Breast cancer risk associated with BRCA1 and BRCA2 in diverse populations. Nature Reviews Cancer. 2007 Dec;7(12):937-48. https://doi.org/10.1038/nrc2054.

Bolton KL, Chenevix-Trench G, Goh C, Sadetzki S, Ramus SJ, Karlan BY, Lambrechts D, Despierre E, Barrowdale D, McGuffog L, Healey S. Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. Jama. 2012 Jan 25;307(4):382-9. doi:10.1001/jama.2012.20.

Bujassoum SM, Bugrein HA, Al‐Sulaiman R. Genotype and phenotype correlation of breast cancer in BRCA mutation carriers and non-carriers. J Cancer Sci Ther. 2017;9(3). DOI: 10.4172/1948-5956.1000442.

Peshkin BN, Alabek ML, Isaacs C. BRCA1/2 mutations and triple negative breast cancers. Breast disease. 2011 Mar 15;32(1-2):25-33. https://doi.org/10.3233/BD-2010-0306.

Streff H, Profato J, Ye Y, Nebgen D, Peterson SK, Singletary C, Arun BK, Litton JK. Cancer incidence in first-and second-degree relatives of BRCA1 and BRCA2 mutation carriers. The oncologist. 2016 Jul 1;21(7):869-74. https://doi.org/10.1634/theoncologist.2015-0354.