Germline Genetics of Prostate Cancer: Prevalence of Risk Variants and Clinical Implications for Disease Management

Abstract

Prostate cancer has entered into the era of precision medicine with the recent approvals of targeted therapeutics (olaparib and rucaparib). The presence of germline mutations has important hereditary cancer implications for patients with prostate cancer, and germline testing is increasingly important in cancer screening, risk assessment, and the overall treatment and management of the disease. In this review, we discuss germline variants associated with inherited predisposition, prostate cancer risk and outcomes. We review recommendations for germline testing, available testing platforms, genetic counseling as well as discuss the therapeutic implications of germline variants relevant to prostate cancer treatments. Understanding the role of germline (heritable) mutations that affect prostate cancer biology and risk as well as the subsequent effect of these alterations on potential therapies is critical as the treatment paradigm shifts towards precision medicine. Furthermore, enhancing patient education tactics and healthcare system infrastructure is essential for the utilization of relevant predictive biomarkers and the improvement of clinical outcomes of patients with prostate cancer or at high risk of developing the disease.

A Polygenic Risk Score Predicts Incident Prostate Cancer Risk in Older Men but Does Not Select for Clinically Significant Disease

“…Although modifiable risk factors (such as smoking) are associated with prostate cancer risk [ 12 , 13 , 14 ], there is limited evidence that prevention is achieved by the cessation of these factors [ 15 , 16 ]. The most significant risk factors for prostate cancer are non-modifiable, such as age, ethnicity [ 17 ], family history [ 18 ], and genetic predisposition [ 19 ]. Therefore, the use of a polygenic risk score (PRS) comprised of common prostate cancer-associated genetic variants has the potential to improve risk prediction, beyond conventional risk factors.…”

Quality of life assessment among ethnically diverse Black prostate cancer survivors: a constructivist grounded theory approach

“…Our study ndings highlight ethnic differences in decision-making dynamics, emphasizing the cultural nuances in treatment choices. Familial involvement, especially spousal involvement in treatment decisions, is crucial as it can impact genetic susceptibility and risk assessment within the family [44,[49][50][51][52]. Various factors also in uenced treatment choices, stressing the importance of personalized care plans and aligning with current medical best practices [53].…”

Genetic Analysis of a Family with Multiple Incidences of Prostate Cancer

“…BRCA1 and BRCA2 genes are tumor suppressors, involved in cellular DNA damage repair. BRCA1 and BRCA2 gene germline mutations are the most common and major drivers of familial Pca [ 2 , 3 , 4 , 7 , 8 ]. The types of BRCA2 gene germline mutations include frameshift (64%), missense (31%), and splicing (5%).…”