{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T12:24:01Z","timestamp":1774441441625,"version":"3.50.1"},"reference-count":51,"publisher":"American Association for Cancer Research (AACR)","issue":"4","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Prostate cancer is the second most common malignancy among men worldwide. Genome-wide association studies have identified 100 risk variants for prostate cancer, which can explain approximately 33% of the familial risk of the disease. We hypothesized that a comprehensive analysis of genetic variations found within the 3\u2032 untranslated region of genes predicted to affect miRNA binding (miRSNP) can identify additional prostate cancer risk variants. We investigated the association between 2,169 miRSNPs and prostate cancer risk in a large-scale analysis of 22,301 cases and 22,320 controls of European ancestry from 23 participating studies. Twenty-two miRSNPs were associated (P &amp;lt; 2.3 \u00d7 10\u22125) with risk of prostate cancer, 10 of which were within 7 genes previously not mapped by GWAS studies. Further, using miRNA mimics and reporter gene assays, we showed that miR-3162-5p has specific affinity for the KLK3 rs1058205 miRSNP T-allele, whereas miR-370 has greater affinity for the VAMP8 rs1010 miRSNP A-allele, validating their functional role.<\/jats:p>\n                  <jats:p>Significance: Findings from this large association study suggest that a focus on miRSNPs, including functional evaluation, can identify candidate risk loci below currently accepted statistical levels of genome-wide significance. Studies of miRNAs and their interactions with SNPs could provide further insights into the mechanisms of prostate cancer risk. Cancer Discov; 5(4); 368\u201379. \u00a92015 AACR.<\/jats:p>\n                  <jats:p>See related commentary by Yousef, p. 351<\/jats:p>\n                  <jats:p>This article is highlighted in the In This Issue feature, p. 333<\/jats:p>","DOI":"10.1158\/2159-8290.cd-14-1057","type":"journal-article","created":{"date-parts":[[2015,2,17]],"date-time":"2015-02-17T23:42:50Z","timestamp":1424216570000},"page":"368-379","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["A Large-Scale Analysis of Genetic Variants within Putative miRNA Binding Sites in Prostate Cancer"],"prefix":"10.1158","volume":"5","author":[{"given":"Shane","family":"Stegeman","sequence":"first","affiliation":[{"name":"1Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Translational Research Institute, Queensland University of Technology, Brisbane, Australia."}]},{"given":"Ernest","family":"Amankwah","sequence":"additional","affiliation":[{"name":"2Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida."}]},{"given":"Kerenaftali","family":"Klein","sequence":"additional","affiliation":[{"name":"3Statistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, Australia."}]},{"given":"Tracy A.","family":"O'Mara","sequence":"additional","affiliation":[{"name":"4Molecular Cancer Epidemiology Laboratory, Genetics and Computational Biology Division, QIMR Berghofer Medical Research Institute, Brisbane, Australia."}]},{"given":"Donghwa","family":"Kim","sequence":"additional","affiliation":[{"name":"5Department of Molecular Oncology, Moffitt Cancer Center, Tampa, Florida."}]},{"given":"Hui-Yi","family":"Lin","sequence":"additional","affiliation":[{"name":"6Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida."}]},{"given":"Jennifer","family":"Permuth-Wey","sequence":"additional","affiliation":[{"name":"2Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida."}]},{"given":"Thomas A.","family":"Sellers","sequence":"additional","affiliation":[{"name":"2Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida."}]},{"given":"Srilakshmi","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"1Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Translational Research Institute, Queensland University of Technology, Brisbane, Australia."}]},{"given":"Rosalind","family":"Eeles","sequence":"additional","affiliation":[{"name":"7The Institute of Cancer Research, London, United Kingdom."},{"name":"8Royal Marsden NHS Foundation Trust, Fulham and Sutton, London and Surrey, United Kingdom."}]},{"given":"Doug","family":"Easton","sequence":"additional","affiliation":[{"name":"9Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Laboratory, Cambridge, United Kingdom."}]},{"given":"Zsofia","family":"Kote-Jarai","sequence":"additional","affiliation":[{"name":"7The Institute of Cancer Research, London, United Kingdom."}]},{"given":"Ali","family":"Amin Al Olama","sequence":"additional","affiliation":[{"name":"9Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Laboratory, Cambridge, United Kingdom."}]},{"given":"Sara","family":"Benlloch","sequence":"additional","affiliation":[{"name":"9Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Laboratory, Cambridge, United 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of Medicine, University of Southern California\/Norris Comprehensive Cancer Center, Los Angeles, California."}]},{"given":"Johanna","family":"Schleutker","sequence":"additional","affiliation":[{"name":"15Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland."},{"name":"16Institute of Biomedical Technology\/BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland."}]},{"given":"B\u00f8rge G.","family":"Nordestgaard","sequence":"additional","affiliation":[{"name":"17Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark."}]},{"given":"Ruth C.","family":"Travis","sequence":"additional","affiliation":[{"name":"18Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom."}]},{"given":"David","family":"Neal","sequence":"additional","affiliation":[{"name":"19Surgical Oncology (Uro-Oncology: S4), University of Cambridge, Addenbrooke's Hospital, Cambridge; Cancer Research UK, Cambridge Research Institute, Cambridge, United Kingdom."}]},{"given":"Paul","family":"Pharoah","sequence":"additional","affiliation":[{"name":"20Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Laboratory, Cambridge, United Kingdom."}]},{"given":"Kay-Tee","family":"Khaw","sequence":"additional","affiliation":[{"name":"21Cambridge Institute of Public Health, University of Cambridge, Cambridge, United Kingdom."}]},{"given":"Janet L.","family":"Stanford","sequence":"additional","affiliation":[{"name":"22Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington."},{"name":"23Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington."}]},{"given":"William J.","family":"Blot","sequence":"additional","affiliation":[{"name":"24International Epidemiology Institute, Rockville, Maryland."}]},{"given":"Stephen","family":"Thibodeau","sequence":"additional","affiliation":[{"name":"25Mayo Clinic, Rochester, Minnesota."}]},{"given":"Christiane","family":"Maier","sequence":"additional","affiliation":[{"name":"26Department of Urology, University Hospital Ulm, Ulm, Germany."},{"name":"27Institute of Human Genetics, University Hospital Ulm, Ulm, Germany."}]},{"given":"Adam S.","family":"Kibel","sequence":"additional","affiliation":[{"name":"28Brigham and Women's Hospital\/Dana-Farber Cancer Institute, Boston, Massachusetts."},{"name":"29Washington University, St. Louis, Missouri."}]},{"given":"Cezary","family":"Cybulski","sequence":"additional","affiliation":[{"name":"30International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland."}]},{"given":"Lisa","family":"Cannon-Albright","sequence":"additional","affiliation":[{"name":"31Division of Genetic Epidemiology, Department of Medicine, University of Utah 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