Cancer Therapy Research Articles

Therapeutic Path to Triple Knockout: Investigating the Pan-inhibitory Mechanisms of AKT, CDK9, and TNKS2 by a Novel 2-phenylquinazolinone Derivative in Cancer Therapy- An In-silico Investigation Therapy.

Blocking the oncogenic Wnt//β-catenin pathway has of late been investigated as a viable therapeutic approach in the treatment of cancer. This involves the multi-targeting of certain members of the tankyrase-kinase family; Tankyrase 2 (TNKS2), Protein Kinase B (AKT), and Cyclin- Dependent Kinase 9 (CDK9), which propagate the oncogenic Wnt/β-catenin signalling pathway. During a recent investigation, the pharmacological activity of 2-(4-aminophenyl)-7-chloro- 3H-quinazolin-4-one was repurposed to serve as a 'triple-target' inhibitor of TNKS2, AKT and CDK9. Yet, the molecular mechanism that surrounds its multi-targeting activity remains unanswered. As such, this study aims to explore the pan-inhibitory mechanism of 2-(4-aminophenyl)-7-chloro-3H-quinazolin- 4-one towards AKT, CDK9, and TNKS2, using in silico techniques. Results revealed favourable binding affinities of -34.17 kcal/mol, -28.74 kcal/mol, and -27.30 kcal/mol for 2-(4-aminophenyl)-7-chloro-3H-quinazolin-4-one towards TNKS2, CDK9, and AKT, respectively. Pan-inhibitory binding of 2-(4-aminophenyl)-7-chloro-3H-quinazolin-4-one is illustrated by close interaction with specific residues on tankyrase-kinase. Structurally, 2-(4-aminophenyl)-7-chloro- 3H-quinazolin-4-one had an impact on the flexibility, solvent-accessible surface area, and stability of all three proteins, which was illustrated by numerous modifications observed in the unbound as well as the bound states of the structures, which evidenced the disruption of their biological function. Prediction of the pharmacokinetics and physicochemical properties of 2-(4-aminophenyl)-7-chloro-3H-quinazolin-4- one further established its inhibitory potential, evidenced by the favourable absorption, metabolism, excretion, and minimal toxicity properties. The following structural insights provide a starting point for understanding the paninhibitory activity of 2-(4-aminophenyl)-7-chloro-3H-quinazolin-4-one. Determining the criticality of the interactions that exist between the pyrimidine ring and catalytic residues could offer insight into the structure-based design of innovative tankyrase-kinase inhibitors with enhanced therapeutic effects.

SMAC Mimetics for the Treatment of Lung Carcinoma: Present Development and Future Prospects.

Uncontrolled cell growth and proliferation, which originate from lung tissue often lead to lung carcinoma and are more likely due to smoking as well as inhaled environmental toxins. It is widely recognized that tumour cells evade the ability of natural programmed death (apoptosis) and facilitates tumour progression and metastasis. Therefore investigating and targeting the apoptosis pathway is being utilized as one of the best approaches for decades. This review describes the emergence of SMAC mimetic drugs as a treatment approach, its possibilities to synergize the response along with current limitations as well as future perspective therapy for lung cancer. Articles were analysed using search engines and databases namely Pubmed and Scopus. Under cancerous circumstances, the level of Inhibitor of Apoptosis Proteins (IAPs) gets elevated, which suppresses the pathway of programmed cell death, plus supports the proliferation of lung cancer. As it is a major apoptosis regulator, natural drugs that imitate the IAP antagonistic response like SMAC mimetic agents/Diablo have been identified to trigger cell death. SMAC i.e. second mitochondria activators of caspases is a molecule produced by mitochondria, stimulates apoptosis by neutralizing/inhibiting IAP and prevents its potential responsible for the activation of caspases. Various preclinical data have proven that these agents elicit the death of lung tumour cells. Apart from inducing apoptosis, these also sensitize the cancer cells toward other effective anticancer approaches like chemo, radio, or immunotherapies. There are many SMAC mimetic agents such as birinapant, BV-6, LCL161, and JP 1201, which have been identified for diagnosis as well as treatment purposes in lung cancer and are also under clinical investigation. SMAC mimetics acts in a restorative way in the prevention of lung cancer.

Hematopoietic stem cell transplantation and cellular therapy in persons living with HIV.

Summarize the latest research of both stem cell transplantation and cellular therapy and present the implications with respect to persons with HIV (PWH), hematologic malignancies, and HIV-1 cure. Allogeneic (alloSCT) and autologous (autoSCT) stem cell transplantation have been shown to be well tolerated and effective regardless of HIV-1 status. AlloSCT leads to a decrease in the HIV-1 latently infected reservoir orders of magnitude below that achieved with antiretroviral therapy (ART) alone. Utilization of CCR5Δ2/Δ32 donors in an alloSCT has resulted in HIV-1 cures. In the last 12 months, three cases of cure have been published, giving further insight into the conditions required for HIV-1 control. Other advances in the treatment of hematological cancers include chimeric antigen receptor T-cell (CART) therapy, which are active in PWH with lymphoma. Here we discuss the advances in SCT and cellular therapy in PWH and cancer. Additionally, we discuss how these technologies are being utilized to achieve HIV-1 cure.

Radioactive iodine therapy for thyroid cancer coexisting with Hashimoto's thyroiditis: a systematic review and meta-analysis.

To investigate the clinical character of differentiated thyroid cancer (DTC) coexisting with Hashimoto's thyroiditis (HT) and provide state-of-art evidence for personalized radioactive iodine-131 therapy (RAIT) for patients coexisting with HT. From January 2000 to January 2023, PubMed, Embase, and Web of Science databases were searched for relevant original articles that published in English on the RAIT efficacy for DTC with HT. RevMan 5.4 and Stata 17.0 were used for data analysis. Eleven studies involving 16605 DTC patients (3321 with HT) were included. HT was more frequent in female (OR: 2.90, 95% confidence interval [CI]: 1.77-4.76, P < .00001). The size of tumour (MD: -0.20, 95% CI: -0.30 to -0.11), extrathyroidal extension rate (OR: 0.77, 95% CI: 0.67-0.90), and metastasis rate (OR: 0.18, 95% CI: 0.08-0.41) were less in HT, but tumour, node, metastasis (TNM) stage had no significant difference among HT and non-HT group. Disease-free survival (DFS) rate (OR: 1.96, 95% CI: 1.57-2.44, P < .00001), 5-year DFS (OR: 1.73, 95% CI: 1.04-2.89, P = .04), and 10-year DFS (OR: 1.56, 95% CI: 1.17-2.09, P = .003) were higher in HT group. The recurrent (OR: 0.62, 95% CI: 0.45-0.83, P = .002), RAIT dosage (MD = -38.71, 95% CI: -60.86 to -16.56, P = .0006), and treatment (MD: -0.13, 95% CI: -0.22 to -0.03, P = .008) were less in HT group. DTC coexisting with HT was associated with less invasion. DFS of HT group was higher than non-HT group after RAIT. Low-dose treatment did not impair the efficacy of RAIT in DTC with HT. Hashimoto's thyroiditis is a risk for DTC, but it minimalizes the progression of cancer and enhance the efficacy of RAIT, which should be considered in personalizing RAIT.

Experiment and Simulation on Mechanical Behavior in 1/2-Scale Demonstration REBCO Coil System of Skeleton Cyclotron for Cancer Therapy

Experiment and Simulation on Mechanical Behavior in 1/2-Scale Demonstration REBCO Coil System of Skeleton Cyclotron for Cancer Therapy

Fabrication and Experiments on a 1/2-Scale Demonstration NI-REBCO Coil System of a Skeleton Cyclotron for Cancer Therapy

Fabrication and Experiments on a 1/2-Scale Demonstration NI-REBCO Coil System of a Skeleton Cyclotron for Cancer Therapy

Molecular Docking of Phytomolecules of Grain Amaranth (Amaranthus hypochondriacus) with AKR1C3Protein Involved in Prostate Cancer in Human Beings

Abstract: This study focuses on exploring how the bioactive compounds found in amaranth— phytol, squalene, and α-tocopherol—could potentially offer medicinal benefits in the context of prostate cancer. The investigation involves a docking study with AKRC13, an important target linked to the control of prostate cancer, aiming to uncover their potential effects against this disease. Costeffective and efficient cancer treatment options are crucial because of the high expenses associated with current cancer therapies as well as their side effects. Amaranth (Amaranthus hypochondriacus) is a pseudocereal crop abundant in squalene, α-tocopherol, and phytol, which shows promising foodbased therapy for various diseases, including cancer. Prostate cancer has been a significant contributor to mortality globally, but the introduction of relugolix has emerged as a crucial therapeutic intervention in its treatment. Hence, this study was conducted to investigate the interactions between grain amaranth bioactive compounds squalene, phytol, and α-tocopherol with AKRC13 protein utilizing a molecular docking approach facilitated by Autodock Vina software. Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB-PDB) (http://www.rcsb.org/) was used for retrieving the 3D crystal structure of the target protein, AKRC13 (PDB ID: 7c7f). The 3D structure of bioactive compounds squalene, phytol, and α-tocopherol were retrieved from the PubChem database, following which Open-Babel was used to change the format from .sdf to .pdb. Furthermore, pharmacokinetics characteristics were also considered along with Lipinski’s rule of five using SwissADME (http://www. Swiss adme.ch/index.php) and pkCSM (http://structure.bioc.cam.ac.uk/pkcsm), indicating their potential as a drug candidate in the initial stage. The potential anticancer properties of the ligands were predicted using PASS software. Following the completion of the docking study, it became evident that α-tocopherol demonstrated the most significant binding energy, followed by squalene and phytol, in comparison to the established drug, relugolix. This implies that the chosen bioactive compounds might possess enzyme-inhibiting properties, indicating their potential for further in vivo anticancer screening using model organisms. The findings serve as stepping stones for advancing the potential use of the discussed bioactive compounds as a potential drug candidate for prostate cancer.

Targeting Lysosomes: A Strategy Against Chemoresistance in Cancer.

Chemotherapy is still the major method of treatment for many types of cancer. Curative cancer therapy is hampered significantly by medication resistance. Acidic organelles like lysosomes serve as protagonists in cellular digestion. Lysosomes, however, are gaining popularity due to their speeding involvement in cancer progression and resistance. For instance, weak chemotherapeutic drugs of basic nature permeate through the lysosomal membrane and are retained in lysosomes in their cationic state, while extracellular release of lysosomal enzymes induces cancer, cytosolic escape of lysosomal hydrolases causes apoptosis, and so on. Drug availability at the sites of action is decreased due to lysosomal drug sequestration, which also enhances cancer resistance. This review looks at lysosomal drug sequestration mechanisms and how they affect cancer treatment resistance. Using lysosomes as subcellular targets to combat drug resistance and reverse drug sequestration is another method for overcoming drug resistance that is covered in this article. The present review has identified lysosomal drug sequestration as one of the reasons behind chemoresistance. The article delves deeper into specific aspects of lysosomal sequestration, providing nuanced insights, critical evaluations, or novel interpretations of different approaches that target lysosomes to defect cancer.

Dietary Plant Metabolites Induced Epigenetic Modification as a Novel Strategy for the Management of Prostate Cancer.

Prostate cancer is a widespread malignancy among men, with a substantial global impact on morbidity and mortality. Despite advances in conventional therapies, the need for innovative and less toxic treatments remains a priority. Emerging evidence suggests that dietary plant metabolites possess epigenetic-modifying properties, making them attractive candidates for prostate cancer treatment. The present work reviews the epigenetic effects of dietary plant metabolites in the context of prostate cancer therapy. We first outline the key epigenetic mechanisms involved in prostate cancer pathogenesis, including histone modifications, DNA methylation, and miRNA or Long Noncoding RNA (lncRNA) dysregulation. Next, we delve into the vast array of dietary plant metabolites that have demonstrated promising anti-cancer effects through epigenetic regulation. Resveratrol, minerals, isothiocyanates, curcumin, tea polyphenols, soy isoflavones and phytoestrogens, garlic compounds, anthocyanins, lycopene, and indoles are among the most extensively studied compounds. These plant-derived bioactive compounds have been shown to influence DNA methylation patterns, histone modifications, and microRNA expression, thereby altering the gene expression allied with prostate cancer progression, cell proliferation, and apoptosis. We also explore preclinical and clinical studies investigating the efficacy of dietary plant metabolites as standalone treatments or in combination with traditional treatments for people with prostate cancer. The present work highlights the potential of dietary plant metabolites as epigenetic modulators to treat prostate cancer. Continued research in this field may pave the way for personalized and precision medicine approaches, moving us closer to the goal of improved prostate cancer management.

Numerical Evaluation of Screening Current-Induced Magnetic Field in 1/2-Scale No-Insulation REBCO Coil System of Skeleton Cyclotron for Cancer Therapy

Numerical Evaluation of Screening Current-Induced Magnetic Field in 1/2-Scale No-Insulation REBCO Coil System of Skeleton Cyclotron for Cancer Therapy

Apoptosis inducing metabolite from marine mangrove actinobacteria VITGAP173.

Marine actinobacteria have proven to be a remarkable source of bioactive metabolites. The present study focused on the isolation of anticancer metabolites from marine actinobacteria. Streptomyces sp. VITGAP173 was found to have promising anticancer activity against breast cancer cell lines (MCF-7). Bioassay-guided fractionation was followed to identify the bioactive metabolites from crude ethyl acetate extract of VITGAP173, which yielded four fractions. Among the four fractions, fraction B exhibited the highest cytotoxic activity against MCF-7 cell lines. Further structural characterization of the fraction was done by FTIR and NMR spectroscopy. The fraction-2 induced cytotoxicity against MCF-7 cell lines and the half maximal inhibition (IC50) value was calculated as 4.7μg/ml. To elucidate the possible mechanism of cell death, MCF-7 cells were treated with fraction-2 for 24 hours and the morphological changes were examined using acridine orange - ethidium bromide (AO/EB) staining. The fraction also increased the reactive oxygen species (ROS) generation (Flow cytometry, DCFH-DA). The molecular mechanism of fraction-induced cell death was analysed by real-time PCR, which revealed that the fraction promotes apoptosis through the CHOP-ATF-4 pathway which is involved in ER stress signalling. The present findings suggest the apoptosis inducing potential of fraction-2 in breast cancer therapy.

Significance and treatment strategies of pathologic complete response after neoadjuvant therapy for gastric cancer

Neoadjuvant therapy, as an important part of comprehensive treatment for locally advanced gastric cancer, has been recommended by various guidelines. Partial locally advanced gastric cancer patients can achieve pathologic complete response (pCR) after neoadjuvant therapy, thus achieving relatively good prognosis. However, there is still controversy over whether complete remission in local pathology can translate into survival benefits, whether pCR is equivalent to cure, and whether subsequent adjuvant therapy is needed. Therefore, how to predict patients who can achieve pathologic complete response after neoadjuvant therapy and identify truly cured patients is the direction of future exploration.

Max Bill's concrete art, as an instrument against irrational thinking and arguments in medicine.

Medicine is currently confronted with an increase in irrationality, and non-scientific thinking manifesting in semingly more holistic and natural treatment options, especially in cancer therapy. The Covid-19 pandemic has demonstrated that irrational beliefs are widely spread even among physicians. Max Bill (1908-94) was a Swiss architect, designer, and artist representing an art style called concrete art that focuses on geometrical abstraction and mathematical thinking. December 9, 2024, will be the 30th death anniversary of Max Bill. The following manuscript describes Max Bill's life and art and tries to offer some suggestions on how his concept of art together with the philosophy of critical rationalism may be excellent instruments to teach medical students and young doctors scientific thinking, and may even be an antidote for irrationality in medicine.

Uveal effusion syndrome following hormonal therapy for prostate cancer: a rare ophthalmic manifestation

Uveal effusion syndrome following hormonal therapy for prostate cancer: a rare ophthalmic manifestation

Language barriers in head and neck cancer: Matched pair analysis of outcomes between non-English speaking and English-speaking patients.

As society grows in cultural diversity, an increasing proportion of patients are expected to be from non-English speaking backgrounds. This study sought to compare the clinical outcomes between non-English speakers and English speakers treated by radiation therapy for head and neck cancer. Seventy-five non-English speaking patients with squamous cell carcinoma of the head and neck were matched to English-speaking controls based on patient and disease variables; clinical outcomes were compared. Non-English speaking patients had inferior 3-year overall survival (64% vs. 77%, p = 0.02) and progression-free survival (59% vs. 73%, p = 0.01) compared with the English-speaking cohort. On logistical regression, non-English-speaking status was associated with a significantly increased risk of overall death (OR = 1.41; 95% CI, 1.09-1.92). Prognosis differed significantly between non-English speaking and English-speaking patients. Culturally tailored programs to address language barriers should be considered to ameliorate disparities in outcome.

NIR Light and GSH Dual-Responsive Upconversion Nanoparticles Loaded with Multifunctional Platinum(IV) Prodrug and RGD Peptide for Precise Cancer Therapy.

Platinum(II) drugs as a first-line anticancer reagent are limited by side effects and drug resistance. Stimuli-responsive nanosystems hold promise for precise spatiotemporal manipulation of drug delivery, with the aim to promote bioavailability and minimize side effects. Herein, a multitargeting octahedral platinum(IV) prodrug with octadecyl aliphatic chain and histone deacetylase inhibitor (phenylbutyric acid, PHB) at axial positions to improve the therapeutic effect of cisplatin was loaded on the upconversion nanoparticles (UCNPs) through hydrophobic interaction. Followed attachment of DSPE-PEG2000 and arginine-glycine-aspartic (RGD) peptide endowed the nanovehicles with high biocompatibility and tumor specificity. The fabricated nanoparticles (UCNP/Pt(IV)-RGD) can be triggered by upconversion luminescence (UCL) irradiation and glutathione (GSH) reduction to controllably release Pt(II) species and PHB, inducing profound cytotoxicity. Both in vitro and in vivo experiments demonstrated that UCNP/Pt(IV)-RGD exhibited remarkable antitumor efficiency, high tumor-targeting specificity, and real-time UCL imaging capacity, presenting an intelligent platinum(IV) prodrug-loaded nanovehicle for UCL-guided dual-stimuli-responsive combination therapy.

The FACT-GP5 as a global tolerability measure: responsiveness and robustness to missing assessments.

The Functional Assessment of Cancer Therapy item (FACT-GP5) has the potential to provide an understanding of global treatment tolerability from the patient perspective. Longitudinal evaluations of the FACT-GP5 and challenges posed by data missing-not-at-random (MNAR) have not been explored. Robustness of the FACT-GP5 to missing data assumptions and the responsiveness of the FACT-GP5 to key side-effects are evaluated. In a randomized, double-blind study (NCT00065325), postmenopausal women (n = 618) with hormone receptor-positive (HR+), advanced breast cancer received either fulvestrant or exemestane and completed FACT measures monthly for seven months. Cumulative link mixed models (CLMM) were fit to evaluate: (1) the trajectory of the FACT-GP5 and (2) the responsiveness of the FACT-GP5 to CTCAE grade, Eastern Cooperative Oncology Group (ECOG) Performance Status scale, and key side-effects from the FACT. Sensitivity analyses of the missing-at-random (MAR) assumption were conducted. Odds of reporting worse side-effect bother increased over time. There were positive within-person relationships between level of side-effect bother (FACT-GP5) and severity of other FACT items, as well as ECOG performance status and Common Terminology Criteria for Adverse Events (CTCAE) grade. The number of missing FACT-GP5 assessments impacted the trajectory of the FACT-GP5 but did not impact the relationships between the FACT-GP5 and other items (except for nausea [FACT-GP2]). Results support the responsiveness of the FACT-GP5. Generally speaking, the responsiveness of the FACT-GP5 is robust to missing assessments. Missingness should be considered, however, when evaluating change over time of the FACT-GP5. NCT00065325. 2003.

Enhanced Skin Penetration and Efficacy: First and Second Generation Lipoidal Nanocarriers in Skin Cancer Therapy.

Skin carcinoma remains one of the most widespread forms of cancer, and its global impact continues to increase. Basal cell carcinoma, melanoma, and squamous cell carcinoma are three kinds of cutaneous carcinomas depending upon occurrence and severity. The invasive nature of skin cancer, the limited effectiveness of current therapy techniques, and constraints to efficient systems for drug delivery are difficulties linked with the treatment of skin carcinoma. In the present era, the delivery of drugs has found a new and exciting horizon in the realm of nanotechnology, which presents inventive solutions to the problems posed by traditional therapeutic procedures for skin cancer management. Lipid-based nanocarriers like solid lipid nanoparticles and nanostructured lipid carriers have attracted a substantial focusin recent years owing to their capability to improve the drug'ssite-specific delivery,enhancing systemic availability,and thus its effectiveness. Due to their distinct structural and functional characteristics, these nanocarriers can deliver a range of medications, such as peptides, nucleic acids, and chemotherapeutics, via different biological barriers, such as the skin. In this review, an effort was made to present the mechanism of lipid nanocarrier permeation via cancerous skin. In addition, recent research advances in lipid nanocarriers have also been discussed with the help of in vitro cell lines and preclinical studies. Being a nano size, their limitations and toxicity aspects in living systems have also been elaborated.

Enhanced Targeted Liposomal Delivery of Imiquimod via Aptamer Functionalization for Head and Neck Cancer Therapy

The incidence of head and neck cancers, particularly those associated with Human Papillomavirus (HPV) infections, has been steadily increasing. Conventional therapies exhibit limitations and drawbacks, prompting the exploration of new strategies over the years, with nanomedicine approaches, especially liposomes gaining relevance. Additionally, the functionalization of liposomes with aptamers enables selective delivery to target cells. For instance, AT11 can serve as a targeting moiety for cancer cells due to its high affinity for nucleolin, a protein overexpressed on the cancer cell’s surface. In this study, liposomes functionalized with AT11 are proposed as drug delivery systems for imiquimod (IQ), aiming to maximize its potential as an anticancer agent for HPV-related cancers.To this end, firstly liposomes were produced through the ethanol injection method, functionalized with AT11-TEG-Cholesteryl, and characterized using dynamic light scattering. The obtained liposomes presented suitable properties for cancer therapy (with sizes from 120-140nm and low polydispersity PDI < 0.16) and were further evaluated in terms of potential anticancer effects. AT11 IQ-associated liposomes allowed a selective delivery of IQ towards a tongue cancer cell line (UPCI-SCC-154) relative to the non-malignant cell line (Het1A). Specifically, they induced a selective reduction of the cell viability (~52% versus ~113%; p < 0.0001), proliferation (~68% versus ~102%; p<0.0001) and increased cell death (~7-fold increase; p < 0.0001)). Additionally, they decreased the migration (from ~24% to ~8%; p < 0.0001) and invasion (to 11%; p = 0.0047) capacities of the cancer cells.In summary, the produced liposomes represent a promising approach to enhance the anticancer potential of IQ in head and neck cancer, particularly in tongue cancer.

IL-10 polymorphism genotypes, haplotypes, and diplotypes are associated with colorectal cancer predisposition and outcome in Tunisian population

Background and aimAs the presence of single nucleotide polymorphisms (SNPs) in the interleukin (IL)-10 gene continues to be a major challenge in the development of effective therapies for digestive cancers, this case-control study was conducted to assess the possible influence of genotype, haplotype and diplotype for two SNPs (-1082A/G (rs1800896) and -592A/C (rs1800872)) located in the promoter region of IL-10 gene on the incidence, severity and prognosis of colorectal cancer (CRC) in Tunisians. MethodsIL-10 gene SNPs were analysed in 130 CRC cases and 165 healthy subjects (HS) using PCR-SSP. ResultsFor the IL-10 -1082A/G SNP, comparison of genotype frequencies between cases and HS groups showed that the G allele significantly reduced CRC risk under the recessive model (GG vs. AA+AG: OR [95%CI]= 0.44 [0.21-0.93], p= 0.03). Conversely, a positive association was observed between the codominant model (AG vs. AA+GG) and high susceptibility (OR [95%CI]= 1.65 [1.02-2.63], p=0.04). After stratification by disease site, the recessive model was also found to reduce susceptibility to colon cancer (OR [95%CI]= 0.18 [0.04-0.72], p=0 .01), while the homozygote model (AA vs. GG) was suggested as a risk factor (OR [95%CI]= 5.16 [1.31-23.26], p= 0.02). Furthermore, the codominant model (AG vs. AA+GG) doubled the risk of rectum cancer (OR [95%CI]= 1.98 [1.07-3.70], p= 0.03). For the IL-10 -592A/C SNP, the codominant model (AC vs. AA+CC) has a protective effect against the development of CRC (OR [95%CI]= 0.59 [0.36-0.94], p= 0.03). The IL-10 gene haplotype was not associated with CRC risk. A stratified analysis by disease site demonstrated that the presence of Hap3 (-1082G and -592C alleles) specifically reduced the risk of developing colon cancer (OR [95%CI]= 0.51 [0.32-0.80], p= 0.003). Moreover, homozygous Hap3/Hap3 diplotype significantly reduced susceptibility to CRC (OR [95%CI]= 0.35 [0.14-0.85], p= 0.02). Interestingly, this diplotype has not been identified in colon cancer patients. Kaplan-Meier analysis showed that the homozygous Hap2/Hap2 diplotype was significantly associated with decreased overall survival (Log-rank: p=0.01). This association was also observed in the colon cancer subgroup (Log-rank: p=0.001). ConclusionOur findings provide preliminary indications that the -1082A/G and -592/AC SNPs within the IL-10 gene may exhibit significant associations with the pathogenesis and prognostic outcomes of CRC. However, further investigations are still warranted to validate and establish the veracity of our findings.