Jul 2026· Iraqi Journal of Science· 0 citations· 35 references
TL;DR
The GA genotype of rs5742621 was significantly associated with elevated IGF-1 levels and increased PCa risk, promoting cell proliferation, inhibiting apoptosis, and accelerating tumor growth.
Abstract
Prostate cancer (PCa) is the second most common cancer among men worldwide. Immunological biomarkers play a crucial role in disease diagnosis, progression, and treatment. This study aimed to investigate the relationship between the rs5742621 (A>G) genetic variant and serum levels of insulin-like growth factor 1 (IGF-1) and other cytokines in patients with PCa compared to healthy controls. A total of 204 patients with PCa (aged 48–80) and 196 healthy controls were enrolled. Blood samples were collected to genotype the rs5742621 variant using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Serum levels of IGF1, macrophage migration inhibitory factor (MIF), CXC motif chemokine ligand 12 (CXCL12), and interleukin-27 (IL-27) were measured using a sandwich immunoassay. The heterozygous GA genotype of rs5742621 was more prevalent among patients with PCa, while the AA genotype was more prevalent in healthy controls. Additionally, serum IGF-1 levels were significantly elevated in PCa patients (median: 110 pg/mL) compared to healthy controls (median: 65 pg/mL; p < 0.001). Similarly, MIF levels were higher in PCa patients (85 pg/mL vs. 45 pg/mL; p < 0.001), as were CXCL12 concentrations (140 pg/mL vs. 40 pg/mL; p < 0.001). In contrast, IL-27 levels were lower in PCa patients (40 pg/mL) than in controls (65 pg/mL; p < 0.001). ROC curve analysis demonstrated that CXCL12 and MIF both achieved perfect diagnostic accuracy (AUC = 1.0), while IGF1 showed excellent diagnostic performance (AUC = 0.979) and IL-27 showed good performance (AUC = 0.903). The GA genotype of rs5742621 was significantly associated with elevated IGF-1 levels and increased PCa risk, promoting cell proliferation, inhibiting apoptosis, and accelerating tumor growth. IGF-1 and related immunological markers may serve as promising diagnostic biomarkers and potential therapeutic targets for prostate cancer.
Background: Breast cancer (BC) remains one of the leading causes of cancer-related morbidity and mortality in women worldwide. Although it has made great progress of early detection and treatment, the related immunogenetic mechanisms are still poorly understood. The present study sought to assess the immune molecular and genetic profile of several selected cytokines together with that of Toll-like receptor 4 (TLR4) in breast cancer patient women; their potential commitment on tumor progression and immune modulation.
Materials and Methods: 65 women patients of breast cancer and same number of age matched healthy control were included in the study. The enzyme linked immuno-sorbent assay (ELISA) was used to measure serum concentrations of IL-6, IL-8, IL-18 and TLR4. The genetic background in cytokine and TLR4 pathways were analyzed for identification of candidate regulatory polymorphisms and pathophysiological significance in breast cancer etiology. All statistical analyses were performed using SPSS v26 with a level of significance p ≤ 0.01.
Results: The study demonstrated significantly elevated serum levels of IL-6, IL-8, IL-18, and TLR4 in breast cancer patients compared to controls (p < 0.01). These findings suggest a strong immuno-inflammatory response and a possible activation of tumor-associated signaling pathways, including JAK/STAT, NF-κB, and TLR-mediated mechanisms. Polymorphisms in IL6, IL8, IL18, and TLR4 genes may influence cytokine expression and predisposition to tumorigenesis.
Conclusion: The immune molecular dysregulation of cytokines and TLR4 appears to contribute to breast cancer progression through both inflammatory and genetic pathways. Integrating genetic polymorphism analysis with cytokine profiling could enhance diagnostic precision and support the development of personalized therapeutic strategies for breast cancer.
Farhan Khaleel Huseein, Ahamed Mahdi Hassan, Hamzah mahmood Najm· Asian Pacific Journal of Can...· 0 citations
Type 1 diabetes (T1D) is an increasingly complex disease influenced by both genetic and environmental triggers, leading to overactivity of the immune system. This preliminary study was conducted to investigate the association of two common cytotoxic T lymphocyte antigen-4 (CTLA-4) variants with T1D susceptibility in the Kurdish population of Iraq. Additionally, we evaluated the correlation between these polymorphisms and anti-GAD antibody positivity, as well as their possible influence on CTLA-4 gene expression. In this study, 52 patients (28 males and 24 females) with T1D and 21 healthy control subjects were genotyped for two (CTLA-4) SNPs, A>G (rs231775) and -318 C>T (rs5742909), using direct DNA sequencing. Furthermore, serum anti-GAD antibody levels were measured by ELISA technique, and the expression of CTLA-4 levels was assessed with quantitative real-time PCR. We discovered that the A>G (rs231775) variant was significantly associated with T1DM. The G allele frequency was significantly higher in type 1 diabetes patients (36.5%, P = 0.0188). The -318 C/T polymorphism showed no significant differences between groups. The GG genotype of the +49A/G polymorphism exhibited a greater prevalence in anti-GAD positive patients relative to negative individuals (77.78% vs. 22.22%), indicating an elevated risk trend (OR = 2.77, 95% CI: 0.51–14.91); however, this finding did not achieve statistical significance (P = 0.28). The (CTLA-4) mRNA gene expression was observed to be non-significantly elevated in T1D relative to the control group (p = 0.1239). Our data indicate that the G allele of the CTLA-4 + 49 A>G variant is associated with increased T1D susceptibility in the Kurdish population, while the genotypic association showed a nominal trend.
H. H. Saed, G. Salih, Hassan M Tawfeeq· Frontiers in Endocrinology· 0 citations
Colorectal Cancer (CRC) is one of the most common malignancies globally, and its increasing prevalence in Iraq is an emerging health problem. This work analyzed the expression profiles of miR-205 (microRNA-205), BCL2 (B-cell lymphoma 2), and YAP1 gene in Iraqi CRC patients to evaluate the potential contribution towards diagnosis and prognosis. Eighty individual CRC and 40 healthy Control patients were recruited. Complete Blood Count (CBC) analysis was performed to assess White Blood Cell (WBC) concentrations, and Interleukin-18 (IL-18) and Interleukin-22 (IL-22) concentrations were determined by Enzyme-Linked Immunosorbent Assay (ELISA). Quantitative real-time Polymerase Chain Reaction (qRT-PCR) was utilized to quantify expression levels of miR-205, BCL2, and YAP1. Diagnostic efficacy was established by performing Receiver Operating Characteristic (ROC) curve analysis, and biomarker associations were evaluated using Pearson correlation. Differences in WBC count levels, IL-18, and IL-22 levels were non-significant in patients vs. controls. In contrast, miR-205 expression was significantly decreased in CRC patients (0.33-fold), whereas BCL2 and YAP1 were significantly up-regulated (1.92-fold and 1.44-fold, respectively). ROC analysis revealed that BCL2 showed the greatest diagnostic activity, with an area under the curve (AUC) of 0.880, and was followed by YAP1 (AUC: 0.736) and miR-205 (AUC: 0.700). There were significant correlations between miR-205/BCL2 and BCL2/YAP1, indicating coordinated roles in apoptosis blocking and tumor growth mechanisms. Collectively these results recommend the tumor suppressive role of miR-205 and the oncogenic role of BCL2 and YAP1 which could explain CRC phenotypes and therapy resistance. Overall, the study d=also suggest the potential of these genes as cancer detection candidate in the Iraqi population even within its limitations.
Asmaa Mahmood Salman Al-Obaidi, Alaa H. Younus, G. J. Shanyoor et al.· Journal of Biological Resear...· 0 citations
Ulcerative colitis (UC) is a common health issue worldwide. IL-38 is a cytokine that was verified to have anti-inflammatory role and associated with many inflammatory and immune disorders. We attempted to evaluate serum level of IL-38 and its polymorphism (rs7599662) in patients with ulcerative colitis. Seventy-eight patients with UC and 78 healthy subjects were enrolled. Serum concentration of IL-38 was assessed via ELISA technique. Rs7599662 of IL-38 was investigated using RT-PCR. When compared to controls, individuals with UC had considerably higher serum levels of IL-38. Also, the mutant TT genotype of rs7599662 was linked significantly to increased risk of UC (p = 0.009).We revealed the association of IL-38 and its polymorphism with increasing susceptibility to UC indicating their possible participation in pathogenesis of UC and the possibility of using IL-38 as a new biomarker and UC therapy target.
S. Hamdy, Alaa Z. Mohamed, O. Abdelaleem et al.· The Egyptian Journal of Inte...· 0 citations
Background: Hypoxia and oxidative stress are central features of cutaneous melanoma biology. Body mass index (BMI) and smoking, both of which can influence systemic hypoxia, inflammation, and oxidative stress, have shown inconsistent associations with melanoma. We investigated the association of the hypoxia-inducible factor-1 alpha gene (HIF1A) rs11549465 (1772 C>T; Pro582Ser) polymorphism, alone and in combination with overweight/obesity or smoking habits, with cutaneous melanoma susceptibility and clinicopathological characteristics. Methods: This observational case–control study included 132 Caucasian Italian patients with cutaneous melanoma and 312 healthy controls. The rs11549465 polymorphism was genotyped by genomic DNA restriction fragment analysis. Logistic regression provided age- and sex-adjusted and mutually adjusted estimates. Results: Genotype and allele frequencies did not differ between patients and controls. Within the melanoma cohort, smoking for ≥20 years remained associated with metastatic disease after adjustment for BMI ≥ 25 kg/m2, age at diagnosis, and sex (aOR = 3.12, p = 0.006), whereas BMI did not (aOR = 1.23, p = 0.612). Compared with healthy controls, metastatic melanoma was independently associated with BMI ≥ 25 kg/m2 (aOR = 2.26, p = 0.010) and smoking for ≥20 years (aOR = 3.85, p < 0.001). Mean pack-years were higher in melanoma patients than controls (9.4 ± 16.7 vs. 5.1 ± 12.2; p = 0.002), and ≥10 and ≥20 pack-years remained associated after age- and sex-adjustment (aOR = 2.19, p = 0.001 and aOR = 3.31, p < 0.001, respectively). Mean pack-years were higher in MetM than NMetM (13.1 ± 21.0 vs. 5.9 ± 10.0; p = 0.013), and ≥20 pack-years was associated with MetM (OR = 3.05, p = 0.017). Adjusted associations with head/neck melanoma (n = 13) were observed for CC plus BMI ≥ 30 kg/m2 (aOR = 9.07, p < 0.001), ≥20 cigarette/day (aOR = 5.96, p = 0.004), ≥20 years smoking (aOR = 6.64, p = 0.003), and other smoking measures. Conclusions: To our knowledge, this is the first report on the interplay between the rs11549465 polymorphism and cutaneous melanoma. HIF1A rs11549465 was not independently associated with melanoma susceptibility. Associations involving smoking, BMI, joint genotype–lifestyle exposures, and anatomical localization had wide confidence intervals and were exploratory; small subgroups and multiple comparisons require cautious interpretation and independent validation.