{"doi":"10.18632/oncotarget.27707","title":"SNPs in the interleukin-12 signaling pathway are associated with breast cancer risk in Puerto Rican women","abstract":"// Angel Núñez-Marrero 1 , Nelly Arroyo 1 , Lenin Godoy 1 , Mohammad Zillur Rahman 1 , Jaime L. Matta 1 and Julie Dutil 1 1 Cancer Biology Division, Ponce Research Institute, Ponce Health Sciences University, Ponce, Puerto Rico Correspondence to: Julie Dutil, email: jdutil@psm.edu Keywords: breast cancer; interleukin-12 (IL-12); IL-12 signaling; genetic association; single nucleotide polymorphisms Received: October 27, 2019     Accepted: July 14, 2020     Published: September 15, 2020 ABSTRACT Interleukin-12 (IL-12) is a proinflammatory cytokine that links innate and adaptive immune responses against tumor cells. Single Nucleotide Polymorphisms (SNPs) in IL-12 genes have been associated with cancer risk. However, limited studies have assessed the role of IL-12 in breast cancer (BC) risk comprehensively, and these were done in European and Asian populations. Here, we evaluated the association of the IL-12 signaling pathway and BC risk in Puerto Rican women. A genetic association study was completed with 461 BC cases and 463 non-BC controls. By logistic regression, IL-12 signaling SNPs were associated with an increased BC risk, including rs2243123 ( IL12A ), rs3761041, rs401502 and rs404733 ( IL12RB1 ), rs7849191 ( JAK2 ), rs280500 ( TYK2 ) and rs4274624 ( STAT4 ). Conversely, other SNPs were associated with reduced BC risk including rs438421 ( IL12RB1 ), rs6693065 ( IL12RB2 ), rs10974947, and rs2274471 ( JAK2 ), rs10168266 and rs925847 ( STAT4 ), and rs2069718 ( IFNG ). Analyses based in hormone receptors such as estrogen (ER) and progesterone (PR) receptors also revealed protective (for SNPs rs3212227- IL12B ; rs3024896 and rs3821236- STAT4 ) and predisposing (for rs2069705- IFNG SNP) BC associations. Haplotype analysis showed a decreased BC risk for IL12B and STAT4 SNPs, whereas increased risk for IL12RB1 SNPs . This study suggests a role of the IL-12 signaling axis and BC risk. SNPs in this pathway may alter IL-12 induced anti-tumor responses and modulate BC predisposition in a population-specific context. Functional studies will be necessary to confirm these findings, which potentially may benefit IL-12 related immunotherapeutic approaches towards BC.","journal":"Oncotarget","year":2020,"id":79720,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":414961,"name":"Nelly Arroyo","orcid":null,"position":1,"is_corresponding":false},{"id":413905,"name":"Lenin Godoy","orcid":"0000-0002-4507-2775","position":2,"is_corresponding":false},{"id":414962,"name":"Mohammad Zillur Rahman","orcid":null,"position":3,"is_corresponding":false},{"id":413906,"name":"Jaime Matta","orcid":"0000-0001-6668-9021","position":4,"is_corresponding":false},{"id":62108,"name":"Julie Dutil","orcid":"0000-0002-0313-6443","position":5,"is_corresponding":false},{"id":413904,"name":"Angel Núñez-Marrero","orcid":"0000-0002-5154-9621","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-18T21:50:57.971597Z","pmid":"32973967","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":[]}