SNPs in the interleukin-12 signaling pathway are associated with breast cancer risk in Puerto Rican women

• Published in: Oncotarget Vol. 11; no. 37; pp. 3420 - 3431
• Main Authors: Núñez-Marrero, Angel, Arroyo, Nelly, Godoy, Lenin, Rahman, Mohammad Zillur, Matta, Jaime L, Dutil, Julie
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 15.09.2020
• Subjects: Research Paper; genetic association; IL-12 signaling; breast cancer; interleukin-12 (IL-12); single nucleotide polymorphisms
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.27707

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 ( ), rs3761041, rs401502 and rs404733 ( ), rs7849191 ( ), rs280500 ( ) and rs4274624 ( ). Conversely, other SNPs were associated with reduced BC risk including rs438421 ( ), rs6693065 ( ), rs10974947, and rs2274471 ( ), rs10168266 and rs925847 ( ), and rs2069718 ( ). Analyses based in hormone receptors such as estrogen (ER) and progesterone (PR) receptors also revealed protective (for SNPs rs3212227- ; rs3024896 and rs3821236- ) and predisposing (for rs2069705- SNP) BC associations. Haplotype analysis showed a decreased BC risk for and SNPs, whereas increased risk for . 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.