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Abstract：
OBJECTIVE: Limited data are available regarding the partner and localizer of BRCA2 (PALB2) in Chinese patients with early breast cancer. This study aimed to assess the spectrum and characteristics of germline PALB2 pathogenic variants in this population.
METHODS: Peripheral blood samples were collected from 1556 patients diagnosed with BRCA1/2-negative early-onset breast cancer. All coding regions and exon‒intron boundaries of the PALB2 genes were screened through next-generation sequencing.
RESULTS: The prevalence of PALB2 pathogenic variants was approximately 0.77% in the cohort. Eleven PALB2 pathogenic variants were identified in twelve participants, including five frameshift mutations and six nonsense mutations. All other variants were detected once, except for PALB2 c.1056_1057del (detected twice). Two PALB2 carriers (2/12, 16.7%) have documented family history of breast cancer and/or ovarian cancer. Patients with a positive family history exhibited a threefold higher possibility of being identified as PALB2 carriers than those without a family history (2% vs. 0.69%), although the difference was not statistically significant (p = 0.178). Compared to non-carriers, PALB2 carriers has a tendency to appear in younger age (≤ 30 years) (25% vs 14.4%), human epidermal growth factor receptor-2 (HER2)-negative status (83.3% vs. 70.2%), and diagnosed with invasive micropapillary carcinoma (16.7% vs 3.1%).
CONCLUSIONS: The prevalence of the germline PALB2 pathogenic variants was approximately 0.77% in Chinese patients with BRCA1/2-negative early-onset breast cancer. Our findings is crucial for understanding population-specific genetic risks and offering insights that can enhance genetic counseling and genetic testing strategies in this population.
METHODS: Peripheral blood samples were collected from 1556 patients diagnosed with BRCA1/2-negative early-onset breast cancer. All coding regions and exon‒intron boundaries of the PALB2 genes were screened through next-generation sequencing.
RESULTS: The prevalence of PALB2 pathogenic variants was approximately 0.77% in the cohort. Eleven PALB2 pathogenic variants were identified in twelve participants, including five frameshift mutations and six nonsense mutations. All other variants were detected once, except for PALB2 c.1056_1057del (detected twice). Two PALB2 carriers (2/12, 16.7%) have documented family history of breast cancer and/or ovarian cancer. Patients with a positive family history exhibited a threefold higher possibility of being identified as PALB2 carriers than those without a family history (2% vs. 0.69%), although the difference was not statistically significant (p = 0.178). Compared to non-carriers, PALB2 carriers has a tendency to appear in younger age (≤ 30 years) (25% vs 14.4%), human epidermal growth factor receptor-2 (HER2)-negative status (83.3% vs. 70.2%), and diagnosed with invasive micropapillary carcinoma (16.7% vs 3.1%).
CONCLUSIONS: The prevalence of the germline PALB2 pathogenic variants was approximately 0.77% in Chinese patients with BRCA1/2-negative early-onset breast cancer. Our findings is crucial for understanding population-specific genetic risks and offering insights that can enhance genetic counseling and genetic testing strategies in this population.
摘要：
目的：关于中国早期乳腺癌患者BRCA2（PALB2）的伴侣和定位器的数据有限。本研究旨在评估该群体种系PALB2致病变异的谱和特征。
方法：收集1556例BRCA1/2阴性早发性乳腺癌患者的外周血样本。通过下一代测序筛选PALB2基因的所有编码区和外显子-内含子边界。
结果：在队列中，PALB2致病变异的患病率约为0.77%。在12名参与者中发现了11种PALB2致病变体，包括五个移码突变和六个无义突变。所有其他变体都被检测到一次，除了PALB2c.1056_1057del（检测两次）。两名PALB2携带者（2/12，16.7％）有乳腺癌和/或卵巢癌家族史。具有阳性家族史的患者被鉴定为PALB2携带者的可能性比没有家族史的患者高三倍（2％vs.0.69%），尽管差异无统计学意义（p=0.178）。与非运营商相比，PALB2携带者有出现在年轻年龄（≤30岁）的趋势（25％vs14.4％），人表皮生长因子受体2（HER2）阴性状态（83.3%vs.70.2%），并诊断为浸润性微乳头状癌（16.7％vs3.1％）。
结论：在中国BRCA1/2阴性早发性乳腺癌患者中，种系PALB2致病变异的患病率约为0.77%。我们的发现对于了解特定人群的遗传风险至关重要，并提供可以增强该人群遗传咨询和遗传检测策略的见解。
方法：收集1556例BRCA1/2阴性早发性乳腺癌患者的外周血样本。通过下一代测序筛选PALB2基因的所有编码区和外显子-内含子边界。
结果：在队列中，PALB2致病变异的患病率约为0.77%。在12名参与者中发现了11种PALB2致病变体，包括五个移码突变和六个无义突变。所有其他变体都被检测到一次，除了PALB2c.1056_1057del（检测两次）。两名PALB2携带者（2/12，16.7％）有乳腺癌和/或卵巢癌家族史。具有阳性家族史的患者被鉴定为PALB2携带者的可能性比没有家族史的患者高三倍（2％vs.0.69%），尽管差异无统计学意义（p=0.178）。与非运营商相比，PALB2携带者有出现在年轻年龄（≤30岁）的趋势（25％vs14.4％），人表皮生长因子受体2（HER2）阴性状态（83.3%vs.70.2%），并诊断为浸润性微乳头状癌（16.7％vs3.1％）。
结论：在中国BRCA1/2阴性早发性乳腺癌患者中，种系PALB2致病变异的患病率约为0.77%。我们的发现对于了解特定人群的遗传风险至关重要，并提供可以增强该人群遗传咨询和遗传检测策略的见解。
