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

Abstract

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 find BRCA1 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.

Absence of Germline BRCA1 c.68_69delAG and c.5266dupC Mutations among Hormone Receptor-negative Breast Cancer Patients: A First Impression at a Tertiary Cancer-care Facility in Tanzania

“…The authors concluded that the c.5266dupC mutation had a substantial contribution to BC incidences in Uzbek population. Hence, the c.5266dupC mutation was postulated to have the founder effect in their population (Abdikhakimov et al 2016) similar to other European countries (Burcoş et al 2013, Hartwig et al 2013) and Southern American country, Brazil (Ewald et al 2011).…”

Determination of genetic predisposition to early breast cancer in women of Kazakh ethnicity

“…There is no evidence to date about the founder effect of BRCA1 c.5278-2del within different populations, whereas BRCA1 c.5266dup was reported as one of the most frequent PVs in Eastern and Central Europe [ 41 ] and North Africa [ 42 ]. It is also discussed as a founder mutation for the development of BC in Uzbek, Ashkenazi Jewish, Tatar and Russian populations [ 43 – 46 ]. Previous studies of the BRCA1 gene showed the absence of the c.5266dup PV in a cohort of 121 Kazakh patients with BC, mean age of 50.3 ± 11.5 years [ 47 ].…”

MICA‐129 Met/Val polymorphism could be a genetic biomarker for Familial Breast Cancer in the Tunisian population

“…Breast cancer risk in mutation carriers is modified by several risk factors that cluster in families, including genetic modifiers of risk that influence mutation penetrance (Chenevix-Trench et al, 2007). One of the major risk factors is a germline mutation in BRCA1 and BRCA2 which have an important role in hereditary breast-ovarian cancer in different populations (Abdikhakimov, Mukaddas, Bakhtiyar, & Shahlo, 2016;Celik et al, 2018;Harris, Morrow, & Bonadonna, 1993;Shahabi et al, 2017). In the Tunisian population, several studies have evaluated the association of these mutations in hereditary breast cancer patients (Belaiba et al, 2018;Fourati et al, 2014;Mahfoudh et al, 2012;Riahi et al, 2015;Troudi et al, 2008).…”