Unravelling genetic variants of a swedish family with high risk of prostate cancer

Abstract

Background: Prostate cancer is the most prevalent cancer in men worldwide. It is a polygenic disease with a substantial proportion of heritability. Identification of novel candidate biomarkers is crucial for clinical cancer prevention and the development of therapeutic strategies. Here, we describe the analysis of rare and common genetic variants that can predispose to the development of prostate cancer.

Methods: Whole-genome sequencing was performed on germline DNA of five Swedish siblings which were diagnosed with prostate cancer. The high-risk variants were identified setting the minor allele frequency < 0.01, CADD > 10 and if tested in PRACTICAL, OR > 1.5, while the low-risk variants were identified minor allele frequency > 0.01, CADD > 10 and if tested in PRACTICAL, OR > 1.1.

Results: We identified 38 candidate high-risk gene variants and 332 candidate low-risk gene variants, where 2 and 14 variants were in coding regions, respectively, that were shared by the brothers with prostate cancer.

Conclusions: This study expanded the knowledge of potential risk factor candidates involved in hereditary and familial prostate cancer. Our findings can be beneficial when applying targeted screening in families with a high risk of developing the disease.

Keywords: Germline; Hereditary; Prostate cancer; Whole-genome sequencing.