Distinct genetic variants of early and late-onset prostate cancer

Abstract

Background: The incidence of early-onset Prostate Cancer (PCa) has increased in the last two decades. Men diagnosed with PCa before age 55 have lower 5-year relative survival rates compared to patients diagnosed later in life. Given the enhanced lethality of early-onset PCa, our aim is to evaluate somatic differences between early and late-onset PCa.

Methods: Patients with PCa were dichotomized into early (< 55 years old) and late-onset PCa (≥ 55 years old). Data is derived from the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE) registry. The GENIE registry contains sequenced tumor samples and clinical data across many cancers a total of 4,546 Patients and 5,740 samples were included with pathologically confirmed prostate adenocarcinoma. The data is derived from 17 cancer centers from 2011 to 2021. Patterns in somatic gene tumor profiles were compared between early-onset and late-onset PCa using a chi-square test and logistic regression.

Results: A total of 452 (11.0%) patients had early-onset PCa while 3640 (89.0%) patients had late-onset PCa. Patients with early-onset PCa were more likely to be Black (12.2% vs. 7.7%) and less likely to have metastatic disease (32.0% vs. 45.0%). After logistic regression, early-onset PCa patients had higher odds of having a mutation in CDK12 [1.51 (95% CI: 1.04-2.22)] and ERF [1.81 (95% CI: 1.02-3.24)]. Patients with a CDK12 mutation were more likely to be Black [1.92 (95% CI: 1.28-2.86); p = 0.002) and to have metastatic disease [1.53 (95% CI: 1.16-2.01); p = 0.003).

Conclusion: Patients with early-onset PCa had distinct somatic gene tumor mutations in ERF and CDK12. Therapeutic targeting of genes associated with early-onset PCa can be potentially useful in future clinical studies.