Center for Precision Medicine, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, No 63 Huangtang Road, Meijiang District, Meizhou, 514031, P. R. China.
Guangdong Engineering Technological Research Center of Clinical Molecular Diagnosis and Antibody Drugs, Meizhou, China.
BMC Med Genomics. 2024 Jan 2;17(1):3. doi: 10.1186/s12920-023-01772-9.
To investigate the prevalence of BRCA1/2 gene variants and evaluate the clinical and pathological characteristics associated with these variants in Chinese Hakka breast cancer patients.
A total of 409 breast cancer patients were analyzed based on next-generation sequencing results, with 337 categorized as non-carriers and 72 as carriers of BRCA1/2 variants. Data on the patients' BRCA1/2 gene mutation status, clinical and pathological characteristics, as well as menstrual and reproductive information, were collected, analyzed, compared, and tabulated. Logistic regression analysis was performed to explore the relationship between clinical characteristics and pathogenic variants.
Among the patients, 72 were identified as carriers of pathogenic or likely pathogenic variants in BRCA1/2, while 337 had likely benign or benign mutations. The BRCA1 c.2635G > T (p. Glu879*) variant was detected at a high frequency, accounting for 12.5% (4/32) of the BRCA1 mutations, while the c.5164_5165del (p.Ser1722Tyrfs*4) variant was common among the BRCA2 mutations, accounting for 17.5% (7/40). It was observed that a higher proportion of BRCA1 carriers had the triple-negative breast cancer subtype, whereas more BRCA2 carriers exhibited estrogen receptor (ER) + and progesterone receptor (PR) + subtypes. Multivariate logistic regression analysis revealed that a family history of cancer (OR = 2.36, 95% CI = 1.00-5.54), bilateral cancer (OR = 4.78, 95% CI 1.61-14.20), human epidermal growth factor receptor 2 (HER2)- (OR = 8.23, 95% CI 3.25-20.84), and Ki67 ≥ 15% (OR = 3.88, 95% CI 1.41-10.65) were associated with BRCA1/2 mutations, with the age at diagnosis, age at menarche, and premenopausal status serving as covariates.
The most common pathogenic variant of the BRCA1 and BRCA2 in breast cancer patients was c.2635G > T and c.5164_5165del, respectively. Additionally, a family history of cancer, bilateral cancer, HER2-, and Ki67 ≥ 15% were identified as independent predictors of BRCA1/2 pathogenic variants.
探讨 BRCA1/2 基因突变在中国客家人群乳腺癌患者中的发生率，并评估与这些突变相关的临床和病理特征。
基于下一代测序结果，对 409 例乳腺癌患者进行分析，其中 337 例为非携带者，72 例为 BRCA1/2 变异携带者。收集、分析、比较和制表患者的 BRCA1/2 基因突变状态、临床病理特征、月经和生殖信息。采用 logistic 回归分析探讨临床特征与致病性变异之间的关系。
在患者中，发现 72 例为 BRCA1/2 致病性或可能致病性变异携带者，337 例为可能良性或良性突变携带者。BRCA1 基因 c.2635G > T(p.Glu879*)变异的检出率较高，占 BRCA1 突变的 12.5%（4/32），而 BRCA2 基因 c.5164_5165del(p.Ser1722Tyrfs*4)变异则较为常见，占 BRCA2 突变的 17.5%（7/40）。观察到 BRCA1 携带者中三阴性乳腺癌亚型比例较高，而 BRCA2 携带者中雌激素受体（ER）+和孕激素受体（PR）+亚型比例较高。多因素 logistic 回归分析显示，癌症家族史（OR=2.36，95%CI=1.00-5.54）、双侧癌（OR=4.78，95%CI=1.61-14.20）、人表皮生长因子受体 2（HER2）-（OR=8.23，95%CI=3.25-20.84）和 Ki67≥15%（OR=3.88，95%CI=1.41-10.65）与 BRCA1/2 基因突变相关，以诊断时年龄、初潮年龄和绝经前状态为协变量。
BRCA1 和 BRCA2 基因突变在乳腺癌患者中最常见的致病性变异分别为 c.2635G > T 和 c.5164_5165del。此外，癌症家族史、双侧癌、HER2-和 Ki67≥15%被确定为 BRCA1/2 致病性变异的独立预测因素。
