{"doi":"10.1038/s41391-021-00378-5","title":"Novel prostate cancer susceptibility gene SP6 predisposes patients to aggressive disease","abstract":"Abstract Prostate cancer (PrCa) is one of the most common cancers in men, but little is known about factors affecting its clinical outcomes. Genome-wide association studies have identified more than 170 germline susceptibility loci, but most of them are not associated with aggressive disease. We performed a genome-wide analysis of 185,478 SNPs in Finnish samples (2738 cases, 2400 controls) from the international Collaborative Oncological Gene-Environment Study (iCOGS) to find underlying PrCa risk variants. We identified a total of 21 common, low-penetrance susceptibility loci, including 10 novel variants independently associated with PrCa risk. Novel risk loci were located in the 8q24 ( CASC8 rs16902147, OR 1.86, p adj = 3.53 × 10 −8 and rs58809953, OR 1.71, p adj = 4.00 × 10 −6 ; intergenic rs79012498, OR 1.81, p adj = 4.26 × 10 −8 ), 17q21 ( SP6 rs2074187, OR 1.66, p adj = 3.75 × 10 −5 ), 11q13 (rs12795301, OR 1.42, p adj = 2.89 × 10 −5 ) and 8p21 (rs995432, OR 1.38, p adj = 3.00 × 10 −11 ) regions. Here, we describe SP6 , a transcription factor gene, as a new, potentially high-risk gene for PrCa. The intronic variant rs2074187 in SP6 was associated not only with overall susceptibility to PrCa (OR 1.66) but also with a higher odds ratio for aggressive PrCa (OR 1.89) and lower odds for non-aggressive PrCa (OR 1.43). Furthermore, the new intergenic variant rs79012498 at 8q24 conferred risk for aggressive PrCa. Our findings highlighted the power of a population-stratified approach to identify novel, clinically actionable germline PrCa risk loci and strongly suggested SP6 as a new PrCa candidate gene that may be involved in the pathogenesis of PrCa.","journal":"Prostate Cancer and Prostatic Diseases","year":2021,"id":192899,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9377,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":323458,"name":"Teuvo L.J. Tammela","orcid":"0000-0002-3529-4649","position":1,"is_corresponding":false},{"id":323460,"name":"Anssi Auvinen","orcid":"0000-0003-1125-4818","position":2,"is_corresponding":false},{"id":240082,"name":"Johanna Schleutker","orcid":"0000-0002-1863-0305","position":3,"is_corresponding":false},{"id":323456,"name":"Csilla Sipeky","orcid":"0000-0002-8853-4722","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-18T23:49:47.463744Z","pmid":"34012061","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}