Page 101 - EJMO-9-1

Eurasian Journal of Medicine and
Oncology
Genomics of breast cancer in Western Kazakhstan

1. Introduction The study of gene mutations associated with BC risk in
Kazakh women will help identify hereditary predispositions
In 2022, female breast cancer (BC) was the second most and facilitate early prevention. The objective of this study
common cancer globally, accounting for approximately is to investigate the polymorphisms of genes associated
2.3 million new cases, or 11.6% of all cancer diagnoses. It with BC in ethnic Kazakh women in Western Kazakhstan,
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was also the fourth leading cause of cancer-related deaths with the goal of identifying hereditary predispositions and
worldwide, with an estimated 666,000 fatalities. BC is informing early prevention strategies.
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the most frequently diagnosed cancer among women and
the leading cause of cancer-related mortality globally. 2. Materials and methods
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Comparing GLOBOCAN data from 2018 and 2020 shows 2.1. Study design and participant criteria
an increase in both BC incidence and mortality. In 2020,
there were 19.1 million new cases and 9.9 million deaths This case–control study was conducted to investigate the genetic
globally due to BC. The age-standardized incidence and risk factors associated with BC in the Kazakh population of
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mortality rates for BC worldwide in 2020 were 47.8 and Western Kazakhstan. Participants included patients diagnosed
13.6 cases per 100,000 population, respectively. According with BC at stages I, II, IIIa, and IIIb, all of whom were over
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to the International Agency for Research on Cancer 18 years of age and Kazakh ethnicity. Exclusion criteria
GLOBOCAN 2020 report, there were 35,366 new cases included pregnant women, patients who require palliative
of malignant neoplasms diagnosed in the Republic of care, and individuals who declined to participate.
Kazakhstan, of which 4,390 (12.4%) were cases of BC. The A total of 299 participants were enrolled, comprising 149
mortality from all malignant neoplasms was 20,959, with women with histologically confirmed BC and 150 control
1,654 (7.9%) deaths due to BC. 2 participants (healthy women with no personal or family

To identify hereditary predispositions to BC and verify history of cancer). Biological samples (peripheral venous
genetic diagnoses in high-risk groups, medical-genetic blood) were collected from all participants following
testing and counseling are conducted for subsequent standard protocols. Informed consent was obtained from
personalized diagnosis, treatment, prognosis, and all participants before their inclusion in the study. The
prevention. BC is a complex disease influenced by both study was conducted in accordance with ethical guidelines
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genetic and non-genetic factors, and, in most cases, lacks and was approved by the Institutional Review Board of
clear inheritance patterns. It is estimated that 40% of West Kazakhstan Marat Ospanov Medical University,
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malignant tumors in various anatomical locations have approval No. 24 (October 3, 2017) in accordance with the
a hereditary etiology, but this proportion is only 10% for Declaration of Helsinki and local ethical guidelines.
BC. Genes associated with BC include BRCA1, BRCA2, 2.2. Sequencing and genotyping
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CHEK2, NBS1, p53, ATM, and others. Inherited mutations
in these genes increase the risk of developing cancer. 2.2.1. Next-generation sequencing
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According to epidemiological studies, only 15 – 20% of Candidate gene sequencing was performed using next-
familial BC cases are largely associated with BRCA1 and generation sequencing (NGS) technology on the Illumina
BRCA2 mutations, whereas the remaining 80 – 85% of platform (MiSeq, Illumina Inc., USA) at the National Center
familial risk is attributed to other known and unknown for Biotechnology, Astana, Kazakhstan. Whole-exome
gene polymorphisms. 7 sequencing was employed to identify SNPs associated with
BC progression. The sequencing was conducted using
In addition to BRCA mutations, there are “non-
BRCA” inherited BC genes, which include both highly paired-end reads with an average depth of 100× to ensure
high coverage of the targeted genomic regions.
penetrant genes (e.g., PALB2, TP53, PTEN, and CDH1)
and moderately penetrant genes (e.g., ATM, BRIP1, and 2.2.2. Genotyping and single nucleotide
CHEK2). Highly penetrant genes are associated with a polymorphism panel selection
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>4-fold increased risk of BC, whereas moderately penetrant
genes confer a 2 – 4-fold increased risk. 10 To focus on genetic variations relevant to BC, we utilized
a custom-designed SNP genotyping panel that included
Single nucleotide polymorphisms (SNPs), found within 113 SNPs previously reported to be associated with BC
or outside genes, are considered low-penetrance variants, risk, prognosis, and progression in the Kazakh ethnic
carrying a 2-fold risk. However, when combined, SNPs population. The selection of SNPs was guided by prior
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can be used to assess polygenic risk, meaning that the genome-wide association studies (GWAS), which were
presence of multiple low-penetrance alleles may increase integrated into the design of the panel. High-throughput
the likelihood of BC development. genotyping was performed using the QuantStudio 12K

Volume 9 Issue 1 (2025) 93 doi: 10.36922/ejmo.5385