CCDC170 as a Candidate Susceptibility Gene in a Korean Family with Hereditary Prostate Cancer

Family history is an important risk factor for prostate cancer. Here, we report a whole-exome sequencing (WES)-based study of a Korean family with five prostate cancer cases over three generations, aimed at identifying novel candidate genes for hereditary prostate cancer. Blood samples were collected from nine male family members across the second and third generations, comprising three affected patients (the two remaining deceased cases could not be sampled) and six unaffected relatives. WES was performed on all nine blood samples and on three matched primary tumor tissues from the affected patients. Variants were annotated with ANNOVAR and filtered by calling quality (≥100), population frequency (<1%), non-silent functional consequence, and concordance between blood and tumor samples across all affected cases. Candidate variants were further annotated by proximity to cancer-associated GWAS Catalog SNPs (within 10,000 bp). No pathogenic or likely-pathogenic variant was identified among well-established hereditary cancer genes. Among the prioritized candidates, a frameshift variant in CCDC170 (c.1146delG, p.E383Sfs*26) was selected as the most promising novel candidate, based on its loss-of-function nature and known association with breast cancer. We propose a frameshift variant in CCDC170 as a novel candidate susceptibility allele for hereditary prostate cancer in this Korean family. Further functional studies are warranted to validate this hypothesis.