{
  "abstract": "Genome-wide association studies (GWAS) have identified numerous non-coding risk variants for prostate and ovarian cancers, yet determining which are regulatorily active and which target genes they control remains challenging. We re-analysed a dinucleotide-barcode massively parallel reporter assay (DiR-seq) of 208 bi-allelic prostate cancer risk single-nucleotide polymorphisms (SNPs) in three prostate cancer cell lines under false-discovery-rate (FDR) control, identifying 50 regulatory SNPs at FDR < 0.10 (30 at FDR < 0.05), including 9 shared by at least two cell lines. Benchmarking standard in-silico functional annotations against this experimental ground truth revealed poor predictive performance (cross-validated ROC-AUC = 0.55-0.59), demonstrating that computational predictions cannot reliably substitute for measured allelic activity. We therefore treated the ovarian analysis as hypothesis-generating. Convergent annotation evidence prioritised 44 of 176 ovarian cancer GWAS leads (31 independent loci); a core of 21 SNPs (17 loci) was stable under alternative weights, leave-one-feature-out scoring and threshold changes, and candidates were enriched in ovarian and fallopian-tube regulatory chromatin (OR = 7.9, FDR = 5 × 10⁻5). Copy-number recurrence at candidate genes agreed between two tumour cohorts (Spearman ρ = 0.75, 95% CI 0.46-0.88) but no more than for chromosome-arm-matched control genes, so this observation is exploratory. Formal colocalisation with full summary statistics supported a shared causal variant for prostate cancer risk and TLCD3A expression at 17p13.3 (PP.H4 = 0.92), whereas the ovarian 17q21.31 signal could not be resolved to a single gene. Transcription-factor motifs disrupted in both cancers were over-represented for the interferon-regulatory factor (IRF) and STAT families (FDR = 3 × 10⁻6), a motif-level hypothesis. In an independent MPRA in primary ovarian epithelial cells, variants disrupting interferon-stimulated response elements (ISREs) were depleted, not enriched, for allele-specific activity (4.6% vs 9.2%; OR = 0.47, nominal p = 0.06, FDR = 0.10), so the IRF/STAT hypothesis was not supported; the same assay confirmed allele-specific activity at one prioritised ovarian candidate, rs2976384 (skew = - 0.67, FDR = 3 × 10⁻5). These results provide an audited prostate regulatory-SNP catalogue, quantify the limits of annotation-based fine-mapping, and offer testable cross-cancer hypotheses.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biology, Faculty of Science, Al-Esraa University, Baghdad, Iraq.",
    "Department of Pharmacology, College of Medicine, Ibn Sina University of Medical and Pharmaceutical Sciences, Baghdad, Iraq.",
    "Department of Biology, Education Faculty, University of Al-Hamdaniya, Mosul, Iraq.",
    "Department of Biotechnology, College of Science, University of Anbar, Anbar, Iraq. ahmed.suleiman@uoanbar.edu.iq."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Wiaam Ahmed Al-Amili"
    },
    {
      "affs": [
        1
      ],
      "name": "Mohammed Ayyed Najm"
    },
    {
      "affs": [
        2
      ],
      "name": "Shatha Saadi Jumaah"
    },
    {
      "affs": [
        3
      ],
      "name": "Ahmed AbdulJabbar Suleiman",
      "orcid": "0000-0001-7427-4483"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4vyssq1nfy05n.bib",
  "cited_by": 0,
  "doi": "10.1186/s44342-026-00087-2",
  "fulltext_url": "https://europepmc.org/articles/PMC13718048",
  "id": "4vyssq1nfy05n",
  "issns": [
    "1598-866X",
    "2234-0742"
  ],
  "landing_url": "https://europepmc.org/article/MED/42958578",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "1311|Genetic Associations and Epidemiology"
    ]
  ],
  "openalex": "W7224387123",
  "pdf_url": "https://europepmc.org/articles/PMC13718048?pdf=render",
  "pmcid": "PMC13718048",
  "pmid": "42958578",
  "published": "2026-10-28",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/4vyssq1nfy05n.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:36Z",
      "native_id": "MED:42958578",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42958578"
    },
    {
      "first_seen": "2026-11-02T12:22:12Z",
      "native_id": "PMC13718048",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s44342-026-00087-2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Genetic Associations and Epidemiology",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Experimental benchmarking of in silico annotations at prostate cancer risk loci and hypothesis-generating cross-cancer prioritisation of ovarian risk variants.",
  "title_text": "Experimental benchmarking of in silico annotations at prostate cancer risk loci and hypothesis-generating cross-cancer prioritisation of ovarian risk variants.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:12Z",
  "url": "https://research.draconitic.com/paper/4vyssq1nfy05n",
  "venue": "Genomics & informatics",
  "versions": []
}