SNPs in the interleukin-12 signaling pathway are associated with breast cancer risk in Puerto Rican women
| Autor: | Angel Núñez-Marrero, Lenin Godoy, Julie Dutil, Nelly Arroyo, Mohammad Zillur Rahman, Jaime Matta |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty genetic association interleukin-12 (IL-12) IL-12 signaling Context (language use) Single-nucleotide polymorphism Biology 03 medical and health sciences single nucleotide polymorphisms 0302 clinical medicine Breast cancer breast cancer Internal medicine IL12A medicine SNP Interleukin 12 receptor beta 1 subunit Genetic association Haplotype medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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