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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.
“To our knowledge, this is the first study using NGS [next-generation sequencing] technology to study the genetic predisposition to early-onset BC women from Kazakhstan and assess their impact on the patients’ clinical outcomes.”
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. The researchers 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.”
Keywords: early-onset breast cancer, triple negative breast cancer, next-generation sequencing, pathogenic variant, Kazakh population
About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open-access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
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