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

// Gulnur Zhunussova 1 , 3 , Nazgul Omarbayeva 2 , 4 , Dilyara Kaidarova 2 , 4 , Saltanat Abdikerim 1 , 3 , Natalya Mit 1 , Ilya Kisselev 1 , Kanagat Yergali 1 , Aigul Zhunussova 1 , Tatyana Goncharova 2 , Aliya Abdrakhmanova 2 , 4 and Leyla Djansugurova 1 , 3 1 Laboratory of Molecular Genetics, Institute of Genetics and Physiology, Almaty 050060, Kazakhstan 2 Kazakh Institute of Oncology and Radiology, Almaty 050060, Kazakhstan 3 Al-Farabi Kazakh National University, Almaty 050060, Kazakhstan 4 Asfendiyarov Kazakh National Medical University, Almaty 050060, Kazakhstan Correspondence to: Gulnur Zhunussova, email: gulnur_j@outlook.com Nazgul Omarbayeva, email: nomarbayeva1@gmail.com Keywords: early-onset breast cancer; triple negative breast cancer; next-generation sequencing; pathogenic variant; Kazakh population Received: May 06, 2023     Accepted: September 21, 2023     Published: October 04, 2023 Copyright: © 2023 Zhunussova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Breast cancer (BC) is the most common type of cancer among women in Kazakhstan. To date, little data are available on the spectrum of genetic variation in Kazakh women with BC. We aimed to identify population-specific genetic markers associated with the risk of developing early-onset BC and test their association with clinical and prognostic factors. The study included 224 Kazakh women diagnosed with BC (≤40 age). Entire coding regions (>1700 exons) and the flanking noncoding regions of 94 cancer-associated genes were sequenced from blood DNA using MiSeq platform. We identified 38 unique pathogenic variants (PVs) in 13 different cancer-predisposing genes among 57 patients (25.4%), of which 6 variants were novel. In total, 12 of the 38 distinct PVs were detected recurrently, including BRCA1 c.5266dup, c.5278-2del, and c.2T>C, and BRCA2 c.9409dup and c.9253del that may be founder in this population. BRCA1 carriers were significantly more likely to develop triple-negative BC (OR = 6.61, 95% CI 2.44–17.91, p = 0.0002) and have family history of BC (OR = 3.17, 95% CI 1.14–8.76, p = 0.03) compared to non-carriers. This study allowed the identification of PVs specific to early-onset BC, which may be used as a foundation to develop regional expertise and diagnostic tools for early detection of BC in young Kazakh women.