PALB2is a tumor suppressor gene. Heterozygous germline pathogenic variants ofPALB2significantly increase the lifetime risk of breast cancer and moderately increase the risk of ovarian and pancreatic cancers. This study analyzed the estimated prevalence ofPALB2variants globally, focusing on East Asian and Korean populations, where limited data were previously available. We examined 125,748 exomes from the Genome Aggregation Database (gnomAD), including 9197 East Asians, and additional data from 5305 individuals in the Korean Variant Archive and 1722 in the Korean Reference Genome Database. AllPALB2variants were interpreted according to guidelines from the American College of Medical Genetics and Genomics and the Clinical Genome Resource. The global prevalence ofPALB2variants was 0.18%, with the highest prevalence in Finnish populations (0.41%) and the lowest in Ashkenazi Jewish populations (0.04%). East Asians had a prevalence of 0.09%. By combining data from Korean genome databases and gnomAD totaling 8936 individuals, the overall prevalence ofPALB2variants in the Korean population was determined to be 0.13%. This study is the first comprehensive investigation ofPALB2variant prevalence in East Asians and Koreans using gnomAD and Korean genome databases. These findings provide essential reference data for future research and highlight the importance of region-specific genetic studies that will inform genetic counseling and hereditary cancer risk management.
PALB2是一种肿瘤抑制基因。其杂合性胚系致病性变异会显著增加个体终生罹患乳腺癌的风险，并适度提高卵巢癌和胰腺癌的发病风险。本研究通过分析全球PALB2变异预估发生率，重点关注既往数据有限的东亚及韩国人群。我们基于基因组聚合数据库（gnomAD）的125,748个外显子组数据（包含9,197例东亚人群样本），并结合韩国变异档案库的5,305例个体数据及韩国参考基因组数据库的1,722例数据进行分析。所有PALB2变异均依据美国医学遗传学与基因组学学会及临床基因组资源联盟指南进行解读。全球PALB2变异发生率为0.18%，其中芬兰人群发生率最高（0.41%），德系犹太人群最低（0.04%）。东亚人群的发生率为0.09%。通过整合韩国基因组数据库与gnomAD共计8,936例样本数据，确定韩国人群PALB2变异总体发生率为0.13%。本研究首次利用gnomAD及韩国基因组数据库对东亚及韩国人群PALB2变异发生率进行系统性研究。这些发现为后续研究提供了关键参考数据，并凸显了区域特异性遗传学研究对遗传咨询和遗传性癌症风险管理的重要指导价值。
肿瘤(癌症)患者之家