Abstract 499P
Background
PALB2 is a tumor suppressor gene. Heterozygous germline pathogenic variants of PALB2 significantly increase the lifetime risk of breast cancer and moderately increase the risk of ovarian and pancreatic cancers. This study analyzed the estimated prevalence of PALB2 variants globally, focusing on East Asian and Korean populations, where limited data were previously available.
Methods
We examined 125,748 exomes from the Genome Aggregation Database (gnomAD), including 9,197 East Asians, and additional data from 5,305 individuals in the Korean Variant Archive and 1,722 in the Korean Reference Genome Database. All PALB2 variants were interpreted according to guidelines from the American College of Medical Genetics and Genomics and the Clinical Genome Resource.
Results
The global prevalence of PALB2 variants 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 8,936 individuals, the overall prevalence of PALB2 variants in the Korean population was determined to be 0.13%.
Conclusions
This study is the first comprehensive investigation of PALB2 variant 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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2021R1I1A1A01049183) and was supported by a Korean Cancer Survivors Healthcare R&D Project grant through the National Cancer Center, funded by the Ministry of Health & Welfare, Republic of Korea, grant number HA23C0419; NCC-23F1850.
Disclosure
All authors have declared no conflicts of interest.