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

Núñez-Marrero, Angel; Arroyo, Nelly; Godoy, Lenin; Rahman, Mohammad Zillur; Matta, Jaime; Dutil, Julie

doi:10.18632/oncotarget.27707

Cited by 12 publications

(9 citation statements)

References 71 publications

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“…Consistent with its important role in regulating the immune response, IL-12 has been confirmed to be tightly associated with immunerelated diseases (36). Epidemiological studies have found that IL-12 polymorphisms are closely related to cancers (37). Due to its ability to activate cytotoxic cells from the immune response, IL-12 is regarded as a potential antitumor drug (38).…”

Section: Discussionmentioning

confidence: 99%

IL-12RB1: a novel immune prognostic biomarker for oral squamous cell carcinoma and linked to PD-1/PD-L1 expression in the tumor immune microenvironment

Zheng¹,

Chen²,

Li³

et al. 2022

Ann Transl Med

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Background: This study aimed to screen and identify potential immune biomarker to predict the prognosis of oral squamous cell carcinoma (OSCC).Methods: Data of OSCC patient from The Cancer Genome Atlas (TCGA) database were downloaded, and the ESTIMATE algorithm was used to calculate stromal and immune scores. Differentially expressed genes (DEGs) between the high and low immune score groups were screened, and Kaplan-Meier survival analysis was performed to identify the DEGs linked to the overall survival (OS) time of OSCC patients. Then, those DEGs were validated in anther cohort. A correlation analysis was used to further screen the prognostic genes which were tightly linked to the expression of programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1). The expression profiles of the candidate genes interleukin 12 receptor subunit beta 1 (IL-12RB1), cytotoxic T-lymphocyte associated protein 4 (CTLA4), and G protein-coupled receptor 25 (GPR25) were identified in the single-cell RNA sequence OSCC dataset from GSE103322. Finally, immunohistochemistry (IHC) and immunofluorescence (IF) were applied to confirm the expression pattern of IL-12RB1 in OSCC tissue microarray. Kaplan-Meier analysis was used to assess the prognostic significance of IL-12RB1 staining score in the malignant and non-malignant cells among the patients. Results:The high immune score group showed better OS compared with that of the low immune scores group. Among 339 DEGs, 90 were identified as being tightly linked to OS time. In the validation set, 23 genes were confirmed to be closely associated with survival prognosis, and the expression levels of IL-12RB1, CTLA4, and GPR25 were commonly associated with the expression of PD-1/PD-L1. The RNA-sequencing showed that IL-12RB1 was expressed in epithelial and immune cells, whereas CTLA4 and GPR25 were relatively poorly expressed in the OSCC tissue. IHC showed that IL-12RB1 was positively expressed in both malignant and non-malignant cells. IF showed that IL-12RB1 was co-expressed with CD3, CD68, PD-1, and PD-L1 on the cytomembrane. Additionally, high score of IL-12RB1 expression in the non-malignant cells was a prognostic risk factor for OS of OSCC.Conclusions: IL-12RB1 was tightly associated with survival of OSCC and with the expression levels of PD-1/PD-L1 in the tumor immune microenvironment.

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Section: Discussionmentioning

confidence: 99%

IL-12RB1: a novel immune prognostic biomarker for oral squamous cell carcinoma and linked to PD-1/PD-L1 expression in the tumor immune microenvironment

Zheng¹,

Chen²,

Li³

et al. 2022

Ann Transl Med

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“…This suggests that these mutations did not present a risk factor for sporadic CRC and that they would rather be associated with a potential protective effect. We observed that genetic studies increasingly show that mutations have a potential protective role in certain multifactorial diseases (Yamamoto-Furusho et al, 2011), in particular cancerous pathologies (Tong et al, 2012;Núñez-Marrero 2020). Globally, association studies of these SNPs with sporadic CRC are rare.…”

Section: Discussionmentioning

confidence: 99%

“…This deficit abolishes both IL-12 and IL-23 signaling pathways (Núñez-Marrero 2020). On the other hand, still concerning breast cancer, certain variations (in particular the rs438421 SNP) would be protective by improving the activity of the IL-12R receptor, thus promoting the production of IFN-γ especially in cytotoxic T cells (van de Vosse et al, 2013;Núñez-Marrero 2020). Furthermore, beyond the mutations favorable to the development of the disease or those which would be protective of it, rare variations and other common ones with an unknown functional effect have been reported for IL-12RB1 (van de Vosse et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

rs401502 and rs11575934 Polymorphisms of the IL-12 Receptor Beta 1 Gene are Protective Against Colorectal Carcinogenesis

et al. 2022

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Background: Colorectal cancer (CRC) is a major public health problem worldwide and in Tunisia. It ranks among the main cancers in terms of incidence and cancer-related cause of death. Its pathogenesis is currently considered to be multifactorial involving genetic and environmental factors. Recent studies have suggested that the gene encoding the β1 subunit of the IL-12 receptor, an important pro-inflammatory cytokine of the anti-tumor response, could be involved in the susceptibility to inherited CRC. Hence, it would be interesting to study the role of single nucleotide polymorphisms (SNPs) within the IL-12RB1 gene (rs401502 and rs11575934) in CRC susceptibility.Aim: Our purpose was to assess whether genetic variants IL-12RB1 +1196G/C (rs401502) and IL-12RB1 +705A/G (rs11575934) within the IL-12RB1 gene are associated with the sporadic CRC risk.Methods: A total of 110 Tunisian patients with sporadic CRC and 141 healthy control subjects were included in this study. Genotyping was performed by high-resolution melting (HRM) analysis. All results were confirmed by direct DNA sequencing or PCR-RFLP methods. Later, the allele frequencies and genotype distribution were established and compared between the control group and CRC patients.Results: The obtained results showed that the two target SNPs were in Hardy–Weinberg equilibrium (HWE) in both patients and controls. Minor allele frequencies of rs401502 SNP were 16.4% in CRC cases and 23.8% in controls. Mutant allele of rs11575934 SNP was present with 21.4% in CRC patients and 29.8% in control group. An association study showed a significant association of two target polymorphisms with CRC, according to the dominant genetic model with OR = 0.577, 95% CI = [0.343 to 0.972], p = 0.038 and OR = 0.547, 95% CI = [0.328 to 0.911], p = 0.02, respectively.Conclusion: In this study, we found, for the first time, a potential protective effect of two SNPs in the IL-12RB1 gene, namely rs401502 and rs11575934, in sporadic colorectal cancer in Tunisians.

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“…To deeply discover new markers related to the etiology, progression and prognosis of lymphoma, we used the Agena Massarray technology platform to detect 25 candidate SNPs of 21 genes (TNFA, IFNG, IFNL3, IL2, IL4, IL6R, IL9, IL10, IL12A, IL22, TGFB1, TBX21/TBET, STAT1, STAT3, STAT5B, STAT6, GATA3, NFKBIA, ITGAM, PTPN22, PARP1) in 245 lymphoma patients and 213 healthy controls 8,10,16–57 . All the 25 candidate SNPs were based on previous research studies about immune‐related genetic polymorphisms on the susceptibility, prognosis, progression and stage of many cancers.…”

Section: Introductionmentioning

confidence: 99%

The genetic polymorphisms of immune‐related genes contribute to the susceptibility and survival of lymphoma

Can

Liu

et al. 2023

Cancer Medicine

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BackgroundThough immunological abnormalities have been proven involved in the pathogenesis of lymphoma, the underlying mechanism remains unclear.MethodsWe investigated 25 single nucleotide polymorphisms (SNPs) of 21 immune‐related genes and explored their roles in lymphoma. The genotyping assay of the selected SNPs was used by the Massarray platform. Logistic regression and Cox proportional hazards models were used to analyze the associations of SNPs and the susceptibility of lymphoma or clinical characteristics of lymphoma patients. In addition, Least Absolute Shrinkage and Selection Operator regression was used to further analyze the relationships with the survival of lymphoma patients and candidate SNPs, and the significant difference between genotypes was verified by the expression of RNA.ResultsBy comparing 245 lymphoma patients with 213 healthy controls, we found eight important SNPs related to the susceptibility of lymphoma, which were involved in JAK–STAT, NF‐κB and other functional pathways. We further analyzed the relationships between SNPs and clinical characteristics. Our results showed that both IL6R (rs2228145) and STAT5B (rs6503691) significantly contributed to the Ann Arbor stages of lymphoma. And the STAT3 (rs744166), IL2 (rs2069762), IL10 (rs1800871), and PARP1 (rs907187) manifested a significant relationship with the peripheral blood counts in lymphoma patients. More importantly, the IFNG (rs2069718) and IL12A (rs6887695) were associated with the overall survival (OS) of lymphoma patients remarkably, and the adverse effects of GC genotypes could not be offset by Bonferroni correction for multiple comparison in rs6887695 especially. Moreover, we determined that the mRNA expression levels of IFNG and IL12A were significantly decreased in patients with shorter‐OS genotypes.ConclusionsWe used multiple methods of analysis to predict the correlations between lymphoma susceptibility, clinical characteristics or OS with SNPs. Our findings reveal that immune‐related genetic polymorphisms contribute to the prognosis and treatment of lymphoma, which may serve as promising predictive targets.

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

Cited by 12 publications

References 71 publications

IL-12RB1: a novel immune prognostic biomarker for oral squamous cell carcinoma and linked to PD-1/PD-L1 expression in the tumor immune microenvironment

IL-12RB1: a novel immune prognostic biomarker for oral squamous cell carcinoma and linked to PD-1/PD-L1 expression in the tumor immune microenvironment

rs401502 and rs11575934 Polymorphisms of the IL-12 Receptor Beta 1 Gene are Protective Against Colorectal Carcinogenesis

The genetic polymorphisms of immune‐related genes contribute to the susceptibility and survival of lymphoma

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