Prostate Cancer

2026-06-27 · Zhang Y, et al. Nature Communications 2026, PMID:42364979

Development and validation of a multiancestry and multitrait polygenic risk score for lung cancer

Zhang Y, et al. (Nature Communications, 2026) is newly in the GWAS Catalog, with 87 associations across 1 trait ("Lung cancer"). The catalogue records its sample as 76,329 cases and 1,886,372 controls. 21 of the study's 87 positions are already on this site — 13 on the Lung Cancer page; 1 on the Prostate Cancer page; 1 on the Celiac Disease page — including rs951984 (near IREB2), rs37005 (LINC01511), rs12907065 (MORF4L1). This item was assembled by code from the catalogue's records; the paper is linked for the rest. PMID:42364979.

2026-08-06 · Multi-omics dissection of FOXA1 reveals cancer-type-specific transcriptional networks and functional risk variants. iScience. 2026. DOI:10.1016/j.isci.2026.117064

How do prostate cancer risk variants actually work? Multi-omics study traces them through FOXA1

GWAS have found many prostate and breast cancer risk loci, but most sit in noncoding DNA where it is unclear how they actually affect cancer biology. This study focused on FOXA1, a 'pioneer' transcription factor that opens chromatin for other regulators in both hormone-associated cancers, integrating its DNA-binding maps, transcriptomes, GWAS loci and eQTL data with functional lab assays. It found that known prostate cancer risk variants are enriched specifically within regions where FOXA1 binds DNA, and that a subset of these variants directly changes how much FOXA1 binds at those sites -- with downstream effects on three specific effector genes, TLE4, USP39 and CPNE1. Functional validation confirmed these FOXA1-regulated targets actually affect prostate cancer cell proliferation and migration in the lab, not just in statistical association. This traces a mechanistic line from inherited noncoding variation, through a specific transcription factor's chromatin binding, to a measurable cancer-cell behavior -- the kind of variant-to-function evidence GWAS hits alone don't provide. This site's prostate cancer page carries 64 variants and its breast cancer page 61; FOXA1 itself, and the three downstream genes it regulates (TLE4, USP39, CPNE1), are not currently among either. The study reports functional-genomics evidence rather than a single lead rsID with a GWAS Catalog-style p-value, so this entry documents the mechanism at the condition level, on the prostate cancer page where the functional validation was specifically done.

2025-07-15 · Development and Validation of a Genome-Wide Association Study Based Polygenic Risk Score for Prostate Cancer in an Asian Population. The World Journal of Men's Health. 2025. DOI:10.5534/wjmh.250056

A 24-SNP risk score built for Taiwanese men predicts prostate cancer with a 34-fold spread between top and bottom risk groups

Most prostate cancer polygenic risk scores (PRS) are built and validated on European-ancestry data, which often transfers poorly to other populations. This study built a PRS specifically for Taiwanese men, using 958 prostate cancer patients and 999 Taiwan Biobank controls after quality control, with independent external validation in 188 additional patients and 188 controls. Out of 87,092 candidate SNPs, 24 were selected for the final model, located in intronic regions of KCNH7, HLA-DQA1 and PRNCR1 among other genes. The PRS achieved an AUC of 0.824 in the primary cohort and 0.757 in the independent validation cohort -- genuinely tested out-of-sample, not just fit to one dataset. Most strikingly, men in the top 25th percentile of the PRS had 34 times the odds of prostate cancer compared to men in the bottom 25th percentile (OR=34.37, P=1.96x10^-52) -- a large, clinically meaningful risk spread specifically calibrated for this population. This site's prostate cancer page carries 64 variants; none of KCNH7, HLA-DQA1 or PRNCR1 are currently among them.

2025-12-12 · U.S. FDA, official approval summary (AMPLITUDE trial, NCT04497844, BRCA2m subgroup n=323)

FDA approves niraparib-abiraterone (Akeega) for BRCA2-mutated prostate cancer

Verified directly against the FDA's own approval summary. On 12 Dec 2025 the FDA approved niraparib plus abiraterone acetate and prednisone (Akeega) for adults with BRCA2-mutated, metastatic, castration-sensitive prostate cancer identified by an FDA-approved companion test. In the AMPLITUDE trial's BRCA2-mutated subgroup (323 of 696 total patients), the combination cut the hazard of radiographic progression or death to 0.46 (95% CI 0.32-0.66) versus placebo plus standard therapy -- median progression-free survival not yet reached versus 26 months on placebo. This page's own text already notes that BRCA2 defects affect PARP-inhibitor eligibility in advanced disease; this is that eligibility becoming a specific, approved combination regimen with trial-level efficacy data, not a new genetic finding.

2026-07-02 · Tolmeijer SH, et al. Germline CDK12 variants in aggressive prostate cancer. Cancer Discovery. 2026. PMID:42392870

Rare inherited CDK12 variants found in five men with lethal metastatic prostate cancer, out of 4,535 tested

Researchers screened 4,535 people with prostate cancer and found five (ages 44-62) carrying an inherited, truncating CDK12 variant -- a mutation that cuts the gene's protein short. These truncating variants were far more common than in the general population: 11.4 times more common than in a large reference database (gnomAD), and 29.6 times more common than in people without cancer. All five had metastatic, lethal disease, and family histories in the two pedigrees tested showed multiple relatives with prostate or ovarian cancer, with the variant confirmed as inherited in both. The authors recommend adding CDK12 to standard hereditary-prostate-cancer testing panels. This is a rare, high-penetrance finding from direct genetic testing, not a common-variant GWAS signal -- no rsID for this exact class of truncating mutation is yet catalogued here.

rs721048 (2p15). Identified in a genome-wide SNP association study of over 23,000 Icelanders with replication in over 15,500 individuals from Europe and the United States; OR 1.15, P = 7.7 x 10^-9. The same study reported rs5945572 on Xp11.22 (OR 1.23, P = 3.9 x 10^-13). The 2p15 variant showed a significantly stronger association with more aggressive than with less aggressive disease — notable because differentiating indolent from consequential disease is the central problem in prostate cancer, and most common variants do not.

Common versus rare. More than a hundred common susceptibility loci are known and polygenic scores have been evaluated for risk stratification, including for targeted screening; they are not standard practice. Separately, germline BRCA2 and to a lesser extent BRCA1, ATM, CHEK2 and mismatch repair genes are associated with earlier onset and more aggressive disease, influence screening discussions in affected families, and — for BRCA2 and other homologous recombination repair defects — affect eligibility for PARP inhibitor therapy in advanced disease. That is the genetics that changes management.

Screening. PSA-based screening reduces prostate cancer mortality modestly at the cost of substantial overdiagnosis; guidelines therefore emphasise informed decision-making, and practice has shifted toward pre-biopsy MRI and active surveillance for low-risk disease. Risk stratification uses PSA, examination, imaging, biopsy grade group and stage; no common variant enters that assessment.