Abstract 2271: Real-World data of germline variants in 5,893 Korean hereditary cancer patients
Authors: Ha-Eun Lee, Sang-Yoon Park, Seeyoun Lee, So-Youn Jung, Myong Cheol Lim, Han-Sung Kang, Jun-Ha Jang, Sun-Young Kong
Journal: Cancer Research (2025)

Abstract Background: The advent of next-generation sequencing (NGS) has significantly enhanced hereditary cancer comprehensive germline genetic testing. While initial efforts targeted BRCA1 and BRCA2, NGS now reveals a broader range of cancer susceptibility genes, highlighting diverse genetic variations. The variability of pathogenic variants (PVs) across ethnic groups underscores the critical importance of population-specific studies. This study evaluates PVs frequency and their clinical relevance in Korean hereditary cancer patients, providing detailed insights into the genetic characteristics in this population. Methods: We analyzed real-world data from 5,893 patients who underwent genetic testing at the National Cancer Center in Korea between 2006 and 2023. Genetic testing included either BRCA1/2 test (n=2,342) or NGS panel testing (n=3,551), with the type of test determined by the physician’s clinical decision and insurance reimbursement criteria. We collected demographic characteristics, personal and family history and analyzed the impact of these factors on PV carrier status. Results: The median age of the patients was 51.3 years (range: 4-92), with 96.3% female. The distribution of diagnosed cancers was as follows: breast cancer (55.8%), ovarian cancer (37.2%), thyroid cancer (2.4%), pancreatic cancer (2.4%), endometrial cancer (2.4%), colorectal cancer (1.9%), prostate cancer (1.7%), lung cancer (0.8%), gastric cancer (0.8%), other cancers (2.8%) and multi-organ cancers (n=677). Among 43.6% patients with a family history of cancer, 87.1% reported a first-degree relative (FDR), 40.5% a second-degree relative (SDR), and 5.2% a third-degree relative (TDR).PVs were observed in 184/1,612 (11.4%) breast cancer, 202/732 (27.5%) ovarian cancer in BRCA1/2 test and 221/1,681(13.1%) breast cancer, 333/1,463 (22.8%) ovarian cancer in NGS panel testing. In patients who underwent NGS panel testing, 606 individuals represented 626 PVs. The genes most commonly affected included BRCA1 (35.8%), BRCA2 (27.3%), RAD51D (4.2%), ATM (3.8%), PALB2 (3.5%), MUTYH (3.0%), CHEK2 (2.4%), MSH2 (2.4%), BRIP1 (2.2%), MLH1 (2.1%), MSH6 (1.9%) and PMS2 (1.8%).In breast and ovarian cancer, multiple organ involvement emerged as a significant risk factor for suspected germline PVs (p &amp;lt;0.01). PV of breast cancer patients was significantly associated with family history of 50.9% with FDR, 13.8% with SDR, and 1.7% with TDR. Conclusion: Our study identified overall 16.6% prevalence of germline PVs in Korean patients and there is a notable finding involving genes other than BRCA1/2, which highlights the broader spectrum of genetic alterations, suggesting the need for greater awareness and preparedness in hereditary cancer.This study was supported by grant from the National Cancer Center. (grant number NCC-2410821). Citation Format: Ha-Eun Lee, Sang-Yoon Park, Seeyoun Lee, So-Youn Jung, Myong Cheol Lim, Han-Sung Kang, Jun-Ha Jang, Sun-Young Kong. Real-World data of germline variants in 5,893 Korean hereditary cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2271.