Germline pathogenic variants in prostate cancer

While most prostate cancer is sporadic, evidence suggests that a significant minority of cases have a hereditary component, and germline variants may play a role in this heritability. In this study, we investigated germline pathogenic variants in prostate cancer patients. All genetic variants were classified using the American College of Medical Genetics and Genomics/Association for Molecular Pathology 2015 guidelines. By retrospectively reviewing patient charts and genetic testing results, we collected clinicopathologic, demographic, and genetic data. Among the 160 prostate cancer patients who met NCCN genetic testing guidelines and underwent germline testing, 41 % had metastatic cancer, while 59 % had localized cancer, mostly high-risk. Nineteen (19) out of the 160 patients (12 %) had a pathogenic or likely pathogenic variant in the following genes: MUTYH (3.1 %), ATM (1.9 %), BRCA2 (1.3 %), CHEK2 (1.3 %), PALB2 (1.3 %), HOXB13 (1.3 %), and 5 other genes (BRIP1, LZTR1, TP53, NTHL1, and NBN), each at a frequency of 0.6 %. There was no significant difference in clinicopathologic data (such as age, serum prostate-specific antigen, Gleason score, and others) between those with a pathogenic or likely pathogenic variant and those without. There was also a lack of significant difference in the number of variants of uncertain significance observed between different racial and ethnic groups. Individuals with a family history of cancer were significantly more likely to have a pathogenic or likely pathogenic variant than those without one (p = 0.002). Overall, our results show the necessity for future research with a larger sample size to better explain the relationship between clinicopathologic data and genetic variants. •Those with a familial history of cancer are more likely to have pathogenic variants.•Trend found between amount of variants of uncertain significance and race/ethnicity.•No significant disparity in number of variants between metastatic and localized cases.