Chu Van Nguyen

Background: 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. Methods: 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. Results: In total, 56 variants were identified in 37 genes associated with BC, including ACVR1B, APC, AR, ARFGEF1, ATM, ATR, BARD1, BLM, BRCA1, BRCA2, CASP8, CASR, CHD8, CTNNB1, ESR1, FAN1, FGFR2, HMMR, KLLN, LZTR1, MCPH1, MLH1, MSH2, MSH3, MSH6, NF1, PMS2, PRKN, RAD54L, RB1CC1, RECQL, SLC22A18, SLX4, SPTBN1, TP53, WRN, and XRCC3 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. Conclusions: 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.

Papillary thyroid carcinoma is the most common type of malignancy in endocrine tumor. Women with breast cancer have an increased risk of developing thyroid cancer. Especially, patients with BRCA1 germline variants, which belong to the DNA DSB repair system, there may be a genetic susceptibility to thyroid cancer. This study investigated a 47-year-old Vietnamese female patient with BRCA1 mutation, namely NM_007294.3 (BRCA1): c.4998insA (p. Tyr1666Terfs), who developed PTC after one year of breast cancer treatment. Factors that are thought to increase the risk of thyroid cancer after breast cancer treatment include treatment methods, hormonal factors, genetic susceptibility, and others. A hypothesis is breast cancer with BRCA1 mutation increases the risk of thyroid cancer. Understanding the relationship between breast and thyroid cancer helps clinicians for well management of both diseases and also contributes to the development of new preventive strategies, diagnostics and therapeutics as so as a new research direction.