The Journal of urology
October 1, 2026 · via Europe PMC
Inherited Predisposition in Steroidogenic Pathways and Risk of Transition to Incurable Prostate Cancer in men with Localized Disease.
Lévesque E, Lacombe L, Saad F, +15 more, Guillemette C.
AI summary — for doctors, generated from the abstract only
Germline variants in steroidogenic genes were associated with progression to lethal prostate cancer, and combining markers predicted outcomes better than single variants.
What was studied
Analysis of 22 SNPs in 10 steroidogenic genes in 1926 men with localised prostate cancer from the PROCURE cohort, median follow-up 9.8 years.
Key findings
- Variants in CYP17A1, SRD5A2, CYP19A1 and CYP1B1 were nominally linked to biochemical recurrence.
- SRD5A2, HSD17B2 and CYP1B1 variants were linked to lethal disease.
- Cumulative marker scores predicted metastasis/CRPC and death more accurately than individual SNPs.
Clinical relevance
Could eventually refine risk stratification.
Who should care
Limitations
Nominal associations without multiple-testing correction mentioned and no external validation shown.
Research stage.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Background
The heterogeneity of prostate cancer (PCa) poses a significant challenge to accurately predict those who will progress to lethal stage. While RNA signatures and somatic DNA alterations can be used to predict clinical outcomes in men with localized PCa, incorporating germline markers may further enhance early prediction of progression to incurable disease.
Patients and methods
We examined germline markers in steroidogenic pathways in the multi-institutional prospective PROCURE cohort of 1926 patients with localized PCa. The association between 22 single nucleotide polymorphisms (SNPs) across 10 steroidogenic genes and 15 hormone levels, biochemical recurrence-free survival (BCRFS), development of metastasis, castration-resistance (CRPC) and PCa specific mortality (PCSM) was assessed along with their potential functional implications.
Results
Thirteen markers were nominally associated with circulating hormone levels at prostatectomy. At a median follow-up (FU) of 9.8 years, variants in CYP17A1, SRD5A2, CYP19A1 and CYP1B1 showed nominal associations with BCRFS, while those located in SRD5A2, HSD17B2 and CYP1B1 were associated with lethal disease. Cumulative associations of these markers predicted time to metastasis/CRPC and fatal outcomes more accurately than individual SNP. Mechanistically, promoter variants in CYP17A1, SRD5A1, and SRD5A2 altered transcriptional activity in cell models, while a CYP1B1 variant was linked to reduced protein expression in primary tumors, likely due to enhanced proteasomal degradation.
Conclusions
Our findings support an association between host genetic variation and circulating hormone levels at surgery, with potential clinical implications for disease progression. These markers represent a step toward the development of non-invasive strategies to refine inherited risk stratification for progression from localized to advanced prostate cancer.
DOI
10.1097/ju.0000000000005334
PMID
42821636
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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