Genetic Variants Associated with Breast Cancer Are Detected by Whole-Exome Sequencing in Vietnamese Patients

<b>Background:</b> Breast cancer (BC) is the most common cancer and the leading cause of cancer death in women. Hereditary BC risk accounts for 25% of all cases. Pathological variants in known BC precursor genes explain only about 30% of hereditary BC cases, while the underlying genetic factors in most families remain unknown. Identifying hereditary cancer risk factors will help improve genetic counseling, cancer prevention, and cancer care. <b>Methods:</b> Here, we used whole-exome sequencing (WES) to identify genetic variants in 105 Vietnamese patients with BC and 50 healthy women. BC-associated variants were screened by the Franklin software and the criteria of the American College of Medical Genetics and Genomics (ACMG) and evaluated based on in silico analysis. <b>Results:</b> In total, 56 variants were identified in 37 genes associated with BC, including <i>ACVR1B</i>, <i>APC</i>, <i>AR</i>, <i>ARFGEF1</i>, <i>ATM</i>, <i>ATR</i>, <i>BARD1</i>, <i>BLM</i>, <i>BRCA1</i>, <i>BRCA2</i>, <i>CASP8</i>, <i>CASR</i>, <i>CHD8</i>, <i>CTNNB1</i>, <i>ESR1</i>, <i>FAN1</i>, <i>FGFR2</i>, <i>HMMR</i>, <i>KLLN</i>, <i>LZTR1</i>, <i>MCPH1</i>, <i>MLH1</i>, <i>MSH2</i>, <i>MSH3</i>, <i>MSH6</i>, <i>NF1</i>, <i>PMS2</i>, <i>PRKN</i>, <i>RAD54L</i>, <i>RB1CC1</i>, <i>RECQL</i>, <i>SLC22A18</i>, <i>SLX4</i>, <i>SPTBN1</i>, <i>TP53</i>, <i>WRN</i>, and <i>XRCC3</i> in 41 patients. Among them, 12 variants were novel, and 10 variants were assessed as pathogenic/likely pathogenic by ACMG and ClinVar. Variants of uncertain significance (VUS) were evaluated using in silico prediction software to predict whether they are likely to cause the disease in patients. <b>Conclusions:</b> This is the first WES study to identify BC-associated genetic variants in Vietnamese patients, providing a comprehensive database of BC susceptibility gene variants. We suggest using WES as a tool to identify genetic variants in BC patients for risk prediction and treatment guidance.