The Potential Contribution of BRCA Mutations to Early Onset and Familial Breast Cancer in Uzbekistan

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Abdulla Abdikhakimov
Mukaddas Tukhtaboeva
Bakhtiyar Adilov
Shahlo Turdikulova


Introuduction: Breast cancer is the most common malignancy in women and affects approximately 1 out of 8 females in the US. Risk of developing breast cancer is strongly influenced by genetic factors. Germ-line mutations in BRCA1 and BRCA2 genes are associated with 5–10% of breast cancer incidence. To reduce the risk of developing cancer and to increase the likelihood of early detection, carriers of BRCA1 or BRCA2 mutations are offered surveillance programs and effective preventive medical interventions. Identification of founder mutations of BRCA1/2 in high risk communities can have a significant impact on the management of hereditary cancer at the level of the national healthcare systems, making genetic testing more affordable and cost-effective. BRCA1 and BRCA2 mutations in breast cancer patients have not been characterized in the Uzbek population. This pilot study aimed to investigate the contribution of BRCA1 and BRCA2 mutation to early onset and familial cases of breast cancer in Uzbekistan.

Methods: A total of 67 patients with breast cancer and 103 age-matched disease free controls were included in this study. Utilizing SYBR Green based real-time allele-specific PCR, we have analyzed DNA samples of  patients with breast cancer and disease free controls to identify the following BRCA1 and BRCA2 mutations: BRCA1 5382insC, BRCA1 4153delA, BRCA1 185delAG, BRCA1 300T>G, BRCA2 6174delT.

Results: Three unrelated samples (4.5%) were found to be positive for the heterozygous 5382insCBRCA1 mutation, representing a possible founder mutation in the Uzbek population, supporting the need for larger studies examining the contribution of this mutation to breast cancer incidence in Uzbekistan.We did not findBRCA1 4153delA, BRCA1 185delAG, BRCA1 300T>G, and BRCA2 6174delT mutations.

Conclusion: This preliminary evidence suggests a potential contribution of BRCA1 5382insC mutation to breast cancer development in Uzbek population. Taking into account a high disease penetrance in carriers of BRCA1 mutation, it seems reasonable to recommend inclusion of the 5382insC mutation test in future research on the development of screening programs for breast cancer prevention in Uzbekistan.

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Abdikhakimov, A., Tukhtaboeva, M., Adilov, B., & Turdikulova, S. (2016). The Potential Contribution of BRCA Mutations to Early Onset and Familial Breast Cancer in Uzbekistan. Central Asian Journal of Global Health, 5(1).


Youlden DR, Cramb SM, Dunn NA, Muller JM, Pyke CM, Baade PD. The descriptive epidemiology of female breast cancer: an international comparison of screening, incidence, survival and mortality. Cancer Epidemiol. 2012;36(3):237-248.

Kurian AW, Fish K, Shema SJ, Clarke CA. Lifetime risks of specific breast cancer subtypes among women in four racial/ethnic groups. Breast Cancer Res. 2010;12(6):R99.

American Cancer Society. 2016; Accessed December 19, 2016.

Petrucelli N, Daly MB, Feldman GL. Hereditary breast and ovarian cancer due to mutations in BRCA1 and BRCA2. Genet Med. 2010;12(5):245-259.

Fackenthal JD, Olopade OI. Breast cancer risk associated with BRCA1 and BRCA2 in diverse populations. Nat Rev Cancer. 2007;7(12):937-948.

Ramus SJ, Gayther SA. The contribution of BRCA1 and BRCA2 to ovarian cancer. Mol Oncol. 2009;3(2):138-150.

Janavicius R. Founder BRCA1/2 mutations in the Europe: implications for hereditary breast-ovarian cancer prevention and control. EPMA J. 2010;1(3):397-412.

Ferla R, Calo V, Cascio S, et al. Founder mutations in BRCA1 and BRCA2 genes. Ann Oncol. 2007;18 Suppl 6:vi93-98.

Murathodzhaev N, Madjidov, WV. Dynamics of cancer indicators in Uzbekistan over the past decade. RPV. 2005:29.

Balmana J, Diez O, Rubio IT, Cardoso F. BRCA in breast cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2011;22 Suppl 6:vi31-34.

Venkitaraman AR. Cancer suppression by the chromosome custodians, BRCA1 and BRCA2. Science. 2014;343(6178):1470-1475.

Yoshida K, Miki Y. Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage. Cancer Sci. 2004;95(11):866-871.

Clark AS, Domchek SM. Clinical management of hereditary breast cancer syndromes. J Mammary Gland Biol Neoplasia. 2011;16(1):17-25.

Granader EJ, Dwamena B, Carlos RC. MRI and mammography surveillance of women at increased risk for breast cancer: recommendations using an evidence-based approach. Acad Radiol. 2008;15(12):1590-1595.

Nelson HD, Pappas M, Zakher B, Mitchell JP, Okinaka-Hu L, Fu R. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: a systematic review to update the U.S. Preventive Services Task Force recommendation. Ann Intern Med. 2014;160(4):255-266.

Evans DG BA, Anderson E, Brain A, Shenton A, Vasen HF, Eccles D, Lucassen A, Pichert G, Hamed H, Moller P, Maehle L, Morrison PJ, Stoppat-Lyonnet D, Gregory H, Smyth E, Niederacher D, Nestle-Krämling C, Campbell J, Hopwood P, Lalloo F, Howell A. Risk reducing mastectomy: outcomes in 10 European centres. J Med Genet. 2009;46:254-258.

Kara NM SM. Prophylactic Mastectomy and Risk-Reducing Salpingo-oophorectomy in BRCA1/2 Mutation Carriers. Current Breast Cancer Reports. Current Breast Cancer Reports. 2012;4(3):199-206.

Chompret A, Nogues C, Stoppa-Lyonnet D. [Oncogenetic consultation for breast cancer]. Presse Med. 2007;36(2 Pt 2):357-363.

Kaufman B, Shapira-Frommer R, Schmutzler RK, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015;33(3):244-250.

Lee JM, Ledermann JA, Kohn EC. PARP Inhibitors for BRCA1/2 mutation-associated and BRCA-like malignancies. Ann Oncol. 2014;25(1):32-40.

Byrski T HT, Dent R, Marczyk E, Jasiowka M, Gronwald J, Jakubowicz J, Cybulski C, Wisniowski R, Godlewski D, Lubinski J, Narod SA. Pathologic complete response to neoadjuvant cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res. 2014;147(2):401-405.

Im KM, Kirchhoff T, Wang X, et al. Haplotype structure in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers. Hum Genet. 2011;130(5):685-699.

World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191-2194.

Sokolenko AP, Mitiushkina NV, Buslov KG, et al. High frequency of BRCA1 5382insC mutation in Russian breast cancer patients. Eur J Cancer. 2006;42(10):1380-1384.

Sokolenko AP, Rozanov ME, Mitiushkina NV, et al. Founder mutations in early-onset, familial and bilateral breast cancer patients from Russia. Fam Cancer. 2007;6(3):281-286.

El-said El-Debaky F, Azab, N, Alhusseini, N, Eliwa, S, Musalam, H. Breast cancer gene 1 (BRCA1) mutation infemale patients with or without family history in Qalubia governorate. Journal of American Science. 2011;7(2):82-93.

Vinodkumar B, Syamala V, Abraham EK, Balakrishnan R, Ankathil R. Germline BRCA1 mutation and survival analysis in familial breast cancer patients in Kerala; South India. J Exp Clin Cancer Res. 2007;26(3):329-336.

Vaidyanathan K, Lakhotia S, Ravishankar HM, Tabassum U, Mukherjee G, Somasundaram K. BRCA1 and BRCA2 germline mutation analysis among Indian women from south India: identification of four novel mutations and high-frequency occurrence of 185delAG mutation. J Biosci. 2009;34(3):415-422.

Yazici H, Bitisik O, Akisik E, et al. BRCA1 and BRCA2 mutations in Turkish breast/ovarian families and young breast cancer patients. Br J Cancer. 2000;83(6):737-742.

Hamel N, Feng BJ, Foretova L, et al. On the origin and diffusion of BRCA1 c.5266dupC (5382insC) in European populations. Eur J Hum Genet. 2011;19(3):300-306.

Kooshyar MM, Nassiri M, Mahdavi M, Doosti M, Parizadeh A. Identification of germline BRCA1 mutations among breast cancer families in Northeastern Iran. Asian Pac J Cancer Prev. 2013;14(7):4339-4345.

Devor E, Abdurakhmonov, I, Zlojutro, M, Millis, MP, Galbraith, JJ, Crawford, MH, Shermatov, S, Buriev, Z, Abdukarimov, A. Gene Flow at the Crossroads of Humanity: mtDNA Sequence Diversity and Alu Insertion Polymorphism Frequencies in Uzbekistan. . The Open Genomics Journal. 2009;2:1-11.

Irwin JA, Ikramov A, Saunier J, et al. The mtDNA composition of Uzbekistan: a microcosm of Central Asian patterns. Int J Legal Med. 2010;124(3):195-204.

Makriyianni I, Hamel N, Ward S, Foulkes WD, Graw S. BRCA1:185delAG found in the San Luis Valley probably originated in a Jewish founder. J Med Genet. 2005;42(5):e27.

Tian JY, Wang HW, Li YC, et al. A genetic contribution from the Far East into Ashkenazi Jews via the ancient Silk Road. Sci Rep. 2015;5:8377.

Leongamornlert D, Mahmud N, Tymrakiewicz M, et al. Germline BRCA1 mutations increase prostate cancer risk. Br J Cancer. 2012;106(10):1697-1701.

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