A common non-cancerous prostate condition whose genetics barely overlap with prostate cancer's — but that shares enough genetic ground with PSA levels to matter for reading a cancer-screening test correctly.
Benign prostatic hyperplasia (BPH), often accompanied by lower urinary tract symptoms (LUTS), is a non-cancerous enlargement of the prostate that affects the majority of elderly men. This page holds 5 variants from a large 2018 genome-wide study.
The study genotyped 20,621 patients with symptomatic BPH/LUTS and 280,541 controls of European ancestry from Iceland and the UK, finding 23 genome-wide significant variants across 14 loci — including this page's rs10054105 (STARD4), rs200476 (HIST1H2BL), rs72878024 (ODF3), rs8853 (TBX3), and rs1638703 (DLEU1). A notable finding: there is little or no overlap between these BPH/LUTS variants and the genetic variants already established for prostate cancer risk — despite both conditions involving the same organ, they appear to be largely separate genetic stories.
Fifteen of the 23 BPH/LUTS variants also associate with serum prostate-specific antigen (PSA) levels, and the study found a strong genetic correlation between BPH/LUTS and PSA (rg=0.77) — a one-standard-deviation increase in a BPH/LUTS polygenic risk score raised PSA levels by 12.9%. This has direct practical relevance: PSA is the same marker used to screen for prostate cancer, and this page's genetics show that PSA elevation can come from BPH/LUTS-related biology alone, with no connection to cancer risk.
2025-07-07 · Frontiers in Immunology 2025, PMID:40692782
Verified directly against the paper's own abstract via Europe PMC (PMID:40692782, Frontiers in Immunology, published 7 July 2025 -- note this is 2025, not 2026, despite showing up in a 2026-dated search snippet; confirmed against the primary source rather than trusted from the summary). Broman et al. used single-cell RNA sequencing to compare immune cells from small versus large prostates in men over 50, against young-donor samples. They found an age-associated CD8+ T cell subset (high Granzyme K, low Granzyme B) that infiltrated aged prostates and positively correlated with International Prostate Symptom Score (IPSS) severity. In lab experiments, granzyme K treatment triggered pro-inflammatory responses in prostate fibroblasts, suggesting a mechanism: aging immune cells may drive BPH symptoms through inflammation, independent of the androgen-driven pathway BPH is traditionally understood through. This is a distinct causal angle from this page's own GWAS variants (STARD4, HIST1H2BL, ODF3, TBX3, DLEU1), which the source study for those loci already noted show little overlap with androgen-pathway biology either -- two separate lines of evidence now both point beyond hormones alone.
BPH/LUTS is diagnosed clinically through symptom assessment, digital rectal exam and, when needed, imaging or urodynamic testing — not by genotype. None of the 5 variants on this page are used by any guideline to diagnose BPH or select treatment.
The loci described above come from a large genetic study of tens of thousands of men. Their clearest practical implication is the genetic link to PSA levels, relevant to correctly interpreting an elevated PSA test — but this page's variants are not a diagnostic test for BPH itself, and a genetic predisposition to elevated PSA through this pathway does not need to be investigated as possible cancer.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Benign Prostatic Hyperplasia comes down to these specific, well-studied positions — not a diagnosis.
STARD4 · rs10054105
See detailed info →DLEU1 · rs1638703
See detailed info →HIST1H2BL · rs200476
See detailed info →ODF3 · rs72878024
See detailed info →TBX3 · rs8853
See detailed info →The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 5 of 5 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
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Benign Prostatic Hyperplasia. MyGeneLog™. https://www.mygenelog.com/conditions/benign-prostatic-hyperplasia
A common, non-cancerous enlargement of the prostate, often accompanied by lower urinary tract symptoms, affecting the majority of elderly men.
Largely no. The 2018 genetic study behind this page found little or no overlap between BPH/LUTS risk variants and established prostate cancer risk variants -- despite both conditions affecting the same organ.
Fifteen of this page's associated variants also raise serum PSA levels, and BPH/LUTS genetics are strongly correlated with PSA overall. PSA elevation from this pathway reflects BPH biology, not necessarily prostate cancer risk.
No. BPH is diagnosed clinically through symptoms and examination. These are population-level genetic findings, not a way to predict an individual case.
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