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Abstract：
Breast cancer is a global health problem. It is an age-dependent disease, but cases of early-onset breast cancer (eBC) are gradually increasing. There are many unresolved questions regarding eBC risk factors, mechanisms of development and screening. Only 10% of eBC cases are due to mutations in the BRCA1/BRCA2 genes, and 90% have a more complex genetic background. This poses a significant challenge to timely cancer detection in young women and highlights the need for research and awareness. Therefore, identifying genetic risk factors for eBC is essential to solving these problems. This study represents an association analysis of 144 eBC cases and 163 control participants to identify genetic markers associated with eBC risks in Kazakh women. We performed a two-stage approach in association analysis to assess genetic predisposition to eBC. First-stage genome-wide association analysis revealed two risk intronic loci in the CHI3L2 gene (p = 5.2 × 10-6) and MGAT5 gene (p = 8.4 × 10-6). Second-stage exonic polymorphisms haplotype analysis showed significant risks for seven haplotypes (p < 9.4 × 10-4). These results point to the importance of studying medium- and low-penetrant genetic markers in their haplotype combinations for a detailed understanding of the role of detected genetic markers in eBC development and prediction.
摘要：
乳腺癌是一个全球性的健康问题。这是一种年龄依赖性疾病，但是早发性乳腺癌（eBC）的病例正在逐渐增加。关于eBC风险因素有许多未解决的问题，发育和筛选机制。只有10％的eBC病例是由于BRCA1/BRCA2基因突变，90%的人有更复杂的遗传背景。这对年轻女性及时检测癌症构成了重大挑战，并强调了研究和意识的必要性。因此,确定eBC的遗传风险因素对于解决这些问题至关重要。这项研究代表了144例eBC病例和163例对照参与者的关联分析，以确定与哈萨克妇女eBC风险相关的遗传标记。我们在关联分析中进行了两阶段方法，以评估对eBC的遗传易感性。第一阶段全基因组关联分析显示，CHI3L2基因（p=5.2×10-6）和MGAT5基因（p=8.4×10-6）中有两个风险内含子位点。第二阶段外显子多态性单倍型分析显示7个单倍型存在显著风险(p<9.4×10-4)。这些结果指出了研究中和低渗透遗传标记在其单倍型组合中的重要性，以详细了解检测到的遗传标记在eBC发育和预测中的作用。
