Risk Of Leukemia Research Articles

Childhood vaccinations and the risk of leukemia: A nationwide cohort study.

A protective effect of childhood vaccinations on leukemia risk, particularly acute lymphoblastic leukemia (ALL), has been hypothesized, though findings are inconsistent. We used a nationwide cohort of Danish children born 1997-2018 (n = 1,360,230), to examine associations between childhood vaccinations and leukemia (<20 years) using registry data (follow-up: December 31, 2018). Cox proportional hazard models with age as the underlying time estimated hazard ratios (HRs) for leukemia (any, ALL, acute myeloid [AML], and other), comparing vaccinated with unvaccinated children. We also accessed the effect of each additional vaccine dose. During 14,536,819 person-years, 771 children were diagnosed with leukemia (74% ALL, 16% AML, and 10% other). Any vaccination was associated with an increased HR for ALL (HR: 2.76; 95% CI: 0.66-11.58), compared to unvaccinated children, with a change in HR of 1.01 (95% CI: 0.96-1.05) per dose. The corresponding HRs for any leukemia, AML, and other leukemia were 1.04 (95% CI: 0.50-2.17), 0.67 (95% CI: 0.18-2.59) and 0.29 (95% CI: 0.09-0.99), with a change in HR of 0.97 (95% CI: 0.94-1.02), 0.92 (95% CI: 0.84-1.00, p = .062) and 0.88 (95% CI: 0.78-1.00, p = .044) per dose. No significant associations were found for vaccination types, except for the pneumococcal vaccine which was associated with a decreased risk of other leukemia (HR: 0.32; 95% CI: 0.14-0.74). In six-months lag analyses, no significant associations were observed, and decreased risks were attenuated. The results provide no strong evidence that childhood vaccinations reduce leukemia risk. The limited number of unvaccinated cases and wide confidence intervals suggest cautious interpretation of some findings.

Association between TLR 2 (rs3804099), TLR4 (rs4986790), and TLR 9 (rs187084) polymorphism and leukemia risk: a systematic reviewand meta-analysis.

Toll-like receptors (TLRs) are crucial components of innate immunity. A specific form of genetic variation in TLR genes may increase the chance of developing leukemia. The present investigation conducted a comprehensive meta-analysis to examine the correlation between three TLR polymorphisms, namely TLR2 (rs3804099), TLR4 (rs4986790), and TLR9 (rs187084), within the leukemia risk group. An in-depth literature search was performed using Web of Science, PubMed, and Google Scholar to identify noteworthy research published in these scientific databases from 2012 to 2024. Research articles were evaluated according to rigorous inclusion criteria, and data was compiled for meta-analysis using Microsoft Excel (Ver. 2013), MedCalc (Ver. 19.3), and RevMan software (Ver. 5.3). Finally, 11 qualified studies were selected for the ongoing investigation, encompassing a combined total of 1315 leukemia casesand 1340 controls. Using a dominant genotype model, the meta-analysis found that the TLR2 (rs3804099) and TLR9 (rs187084) polymorphisms were strongly linked to higher risk of leukemia, with ORsof 2.042 (95% CI: 1.35-3.08, p = 0.001) and 1.38 (95% CI: 1.14-1.67, p = 0.001) respectively. Notably, the TLR4 (rs4986790) polymorphism did not exhibited any substantial correlation with the incidence of leukemia. The results indicate that variations in TLR2 and TLR9 genes could be considered a novel genetic biomarker for the leukemia development, highlighting their potential use in risk assessment and targeted therapies. This emphasizes the possibility of using these variations in evaluating risk and developing targeted remedies. However, greater research capacities are required to research into the fundamental mechanisms and authenticate these trends inother populations.

A first-born twin has a higher risk of acute leukemia in a population-based assessment of cancer in twins in California, and a lower than anticipated rate of twin concordance.

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Molecular measurable residual disease before transplantation independently predicts survival and relapse risk in adult lysine methyltransferase 2a-rearranged acute myeloid leukemia.

Patients with lysine methyltransferase 2a (KMT2A)-rearranged (KMT2A-r) acute myeloid leukemia (AML) are assigned to intermediate-risk and adverse-risk categories at diagnosis. However, the value of molecular measurable residual disease (MRD) status in patients who have KMT2A-r AML before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult cohorts has rarely been evaluated. Patients with KMT2A-r AML who achieved complete remission and subsequently underwent allo-HSCT between January 2015 and January 2023 were included in this analysis. Real-time quantitative polymerase chain reaction was used to detect molecular MRD in bone marrow samples. The end points were overall survival (OS), leukemia-free survival (LFS), the cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM). Pretransplantation molecular MRD was identified in 52 of 125 patients (42%) with KMT2A-r AML. The presence of KMT2A-r MRD was associated with inferior 3-year OS (51% vs. 82%; p<.001), LFS (42% vs. 81%; p<.001), CIR (33% vs. 12%; p<.001), and NRM (11% vs. 5%; p=.12). In multivariate models, molecular MRD status before transplantation independently predicted OS, LFS, and CIR. Thesurvival of adult patients with KMT2A-r AML was heterogeneous, depending onthe KMT2A translocation partners, and was more favorable in patients who hadt(9;11) and t(10;11) than in those who had t(11;19) and t(6;11). In addition, flow cytometry-based MRD analysis conferred no additional prognostic value to the results of molecular MRD status. Residual KMT2A-r before allo-HSCT independently predicts the risk of survival and relapse, and donor lymphocyte infusion or posttransplantation maintenance therapies should be considered for patients who have AML with detectable molecular MRD.

A foundation model of transcription across human cell types.

Transcriptional regulation, which involves a complex interplay between regulatory sequences and proteins, directs all biological processes. Computational models of transcription lack generalizability to accurately extrapolate to unseen cell types and conditions. Here we introduce GET (general expression transformer), an interpretable foundation model designed to uncover regulatory grammars across 213 human fetal and adult cell types1,2. Relying exclusively on chromatin accessibility data and sequence information, GET achieves experimental-level accuracy in predicting gene expression even in previously unseen cell types3. GET also shows remarkable adaptability across new sequencing platforms and assays, enabling regulatory inference across a broad range of cell types and conditions, and uncovers universal and cell-type-specific transcription factor interaction networks. We evaluated its performance in prediction of regulatory activity, inference of regulatory elements and regulators, and identification of physical interactions between transcription factors and found that it outperforms current models4 in predicting lentivirus-based massively parallel reporter assay readout5,6. In fetal erythroblasts7, we identified distal (greater than 1 Mbp) regulatory regions that were missed by previous models, and, in B cells, we identified a lymphocyte-specific transcription factor-transcription factor interaction that explains the functional significance of a leukaemia risk predisposing germline mutation8-10. In sum, we provide a generalizable and accurate model for transcription together with catalogues of gene regulation and transcription factor interactions, all with cell type specificity.

Association of DNA Repair XRCC1 Gene Polymorphism with Leukemia

A group of cancerous diseases of the blood and bone marrow known as leukemias are life-threatening. It is crucial to recognize the leukemic cells lineage when making a diagnosis of leukemia because treatment for the disease depends on whether the cells are myeloid or lymphoid. As per the Observation There is total 300 blood samples in which 150 were leukemic patients and 150 were healthy person. The genotype distribution frequencies of the XRCC1 gene's SNP rs25487 results demonstrate a highly significant connection between heterozygous (GA) rs25487 of the XRCC1 gene and an increased risk of leukemia up to 2-folds (OR=2.52; 95% CI=1.51- 4.20; p=0.0004). The scenario is identical when it comes to homozygous mutant (AA), which also shown a highly significant connection with a reduced risk of leukemia and performs a protective role (OR=0.40; 95% CI=0.23-0.70; p=0.0014). The combined genotype model of mutant and hetero of rs25487 demonstrated a weakly non-significant correlation with leukemia (OR=1.14; 95% CI=0.72-1.82; p=0.5618). This study intended to look at the connection between leukemia risk regulation and XRCC1 polymorphisms, as well as the conceivable relationship between leukemia patients and the XRCC1 polymorphism (rs25487). It was determined that rs25487 was linked to a higher risk of leukemia in people

Causal relationship between branched-chain amino acids and leukemia risk: insights from a two-sample Mendelian randomization study

ABSTRACT Background Branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, are essential amino acids involved in protein synthesis, energy metabolism, and immune regulation. While BCAAs are known to influence cancer biology, their role in leukemia remains unclear. This study employs Mendelian randomization (MR) analysis to explore the causal relationship between BCAA levels and four leukemia subtypes: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML). Methods Data from genome-wide association studies (GWAS) were used to select single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for BCAA levels. The inverse-variance weighted (IVW) method served as the primary analytical approach, with heterogeneity assessed via Cochran’s Q test and pleiotropy through MR-Egger intercept. Sensitivity analysis was performed using leave-one-out analysis. Results A significant inverse association was observed between total BCAA levels, leucine, valine, and ALL risk. Total BCAA levels showed an odds ratio (OR) of 0.16 (95% CI: 0.05–0.54, p=0.003), leucine 0.17 (95% CI: 0.04–0.61, p=0.007), and valine 0.21 (95% CI: 0.07–0.61, p=0.004). No significant associations were found for AML, CLL, or CML. Conclusion This study suggests that BCAAs, particularly leucine and valine, may protect against ALL, offering insights into leukemia metabolic regulation and potential targets for prevention and therapy.

HIV-1 Viremia and Cancer Risk in 2.8 Million People: the South African HIV Cancer Match Study

Abstract Background Most research on HIV-1 viremia and cancer risk is from high-income countries. We evaluated the association between HIV-1 viremia and the risk of various cancer types among people with HIV (PWH) in South Africa. Methods We analysed data from the South African HIV Cancer Match study, based on laboratory measurements from the National Health Laboratory Services and cancer records from the National Cancer Registry from 2004-2014. Using Cox proportional hazards models, we estimated hazard ratios (HR) for cancer incidence per unit increase in time-updated Log10 HIV-1 RNA viral load copies/mL. We created partially adjusted (sex, age, calendar year) and fully adjusted models (additionally including time-updated CD4 count). Results We included 2,770,200 PWH with 10,175 incident cancers; most common were cervical cancer (N=2,481), Kaposi sarcoma (N=1,902), breast cancer (N=1,063), and non-Hodgkin lymphoma (N=863). Hazard ratios for the association of HIV-1 viremia and cancer risk changed after partial and full adjustment and were generally attenuated for infection-related cancers but tended to increase for infection-unrelated cancers. In the fully adjusted model, HIV-1 viremia was associated with an increased risk of Kaposi sarcoma (HR per unit increase in Log10 HIV-1 RNA viral load: 1.38, 95% CI 1.35-1.42), leukemia (HR: 1.28, 95% CI 1.13-1.45), non-Hodgkin lymphoma (HR: 1.24, 95% CI 1.19-1.29), conjunctival cancer (HR: 1.19, 95% CI 1.11-1.25), and colorectal cancer (HR: 1.11, 95% CI 1.02-1.21). Associations with other cancer types were weaker or absent. Conclusions Our findings underline the importance of sustained viral suppression for cancer prevention among PWH in South Africa.

Beyond the Burn: Leukemia Threats Following Radioactive Iodine Ablation Therapy for Thyroid Cancer

Background: Radioactive iodine (RAI) ablation therapy is a common minimally invasive treatment for patients diagnosed with differentiated thyroid cancer (DTC). Although previous studies have identified a link between RAI and the mortality from secondary solid cancers, the connection between RAI and leukemia remains under-researched. This study investigated the differential risk of leukemia and its subtypes in DTC patients following RAI treatment. Methods: DTC patients from the Surveillance, Epidemiology, and End Results (SEER) Registry 17 (2000–2019) were analyzed. The standard incidence ratio (SIR) and excess risk (ER) compared to the reference population were calculated. Results: Out of 196,569 DTC patients, 1381 patients developed various types of hematological malignancies. Leukemia was diagnosed in 508 of these patients, and it had the highest risk among the malignancies studied, with an SIR of 1.74 (95%CI: 1.59–1.9). The RAI group had an SIR of 2.12 (95%CI: 1.87–2.39), while the non-RAI group had an SIR was 1.45 (95%CI: 1.37–1.52) (p &lt; 0.001). Those diagnosed before the age of 55 years had a conspicuously elevated risk (SIR 2.74) compared to those diagnosed at 55 years or older (SIR 1.53). American Indian/Alaska Native survivors manifested a pronounced leukemia risk with an SIR of 7.63 (95%CI: 2.46–17.8). Conclusions: RAI treatment increased the risk of developing leukemia when serving as adjuvant therapy in surgical patients (SIR 2.12). There exists a significant association between RAI treatment in DTC patients and the incidence of leukemia. This susceptibility seems to be modulated by factors including time since diagnosis, age, gender, and racial background.

Inhibition of JAK2 and MDM2 to treat secondary acute myeloid leukemia evolving from myelofibrosis

AbstractMyelofibrosis (MF) is characterized by splenomegaly, extramedullary hematopoiesis, bone marrow fibrosis, anemia, constitutional symptoms, and risk of secondary acute myeloid leukemia (sAML). The prognosis for sAML is very poor, with a median survival of less than 6 months, largely due to its resistance to treatment. The main cause of death in MF patients is leukemic transformation. Leukemic transformation requires genetic mutations, such as the JAK2 V617F mutation, which is present in most sAML patients. Mutations in TP53 or the amplification of genes that negatively regulate p53 occur more frequently in sAML than in de novo acute myeloid leukemia (AML). Currently, the treatment of sAML poses a substantial challenge to the medical community. This review explored the potential of targeting JAK2 and MDM2 for the treatment of secondary AML caused by myelofibrosis. This review describes the research on sAML in relation to JAK2 and p53, outlines the interaction between JAK2, p53, mtP53, and MDM2, summarizes the effectiveness of JAK2 and MDM2 inhibitors, and advocates a combined approach using JAK2 and MDM2 inhibitors as a potential treatment strategy for sAML evolving from myelofibrosis. Inhibition of JAK2 and MDM2 may help improve the specificity and efficiency of sAML treatment and address drug resistance.

Alpha-1 antitrypsin deficiency associated with increased risks of skin cancer, leukemia, and hepatic cancer: A nationwide cohort study.

α1-Antitrypsin deficiency is characterized by elevated elastase activity and excessive elastin degradation, which may impact cancer development and progression. We tested the hypothesis that individuals with α1-antitrypsin deficiency have increased susceptibility to cancer in the Danish population. In a nationwide nested study, we identified 2702 individuals with α1-antitrypsin deficiency and 26,750 control subjects without α1-antitrypsin deficiency matched on age, sex, and municipality. We recorded admissions due to cancer as outcomes during a median follow-up of 62 years. Individuals with α1-antitrypsin deficiency versus control subjects had an increased hazard of skin cancer (2.18, 95%CI: 1.81-2.63), leukemia (1.76, 1.12-2.79), liver cancer (3.91, 2.23-6.85), and cancer overall (1.25, 1.13-1.38). Corresponding hazard ratios when the entire Danish population was used as control group were 3.02 (2.55-3.58), 1.83 (1.19-2.81), 4.46 (2.74-7.28), and 1.45 (1.31-1.59). When the analysis was stratified according to comorbidities, the hazard for skin cancer was higher in those with chronic obstructive pulmonary disease (COPD) (3.59, 2.60-4.95) and skin disease (2.93, 2.19-3.92) but remained elevated in those without any of these diseases. Hazards for skin cancer in individuals with α1-antitrypsin deficiency were similar when stratified by liver cirrhosis and ischemic heart disease (ps for interaction: ≥0.76). Hazards for liver cancer in individuals with α1-antitrypsin deficiency versus control subjects were similar when stratified according to liver cirrhosis, COPD, skin disease, and ischemic heart disease (ps for interaction: ≥0.13). Individuals with α1-antitrypsin deficiency have increased risks of skin cancer, leukemia, and liver cancer in the Danish population.

Maternal use of hormonal contraception and risk of childhood leukemia: A Scandinavian population-based cohort study.

Maternal hormonal contraception use has been associated with childhood leukemia risk. However, studies are few and often based on self-reported information. Using registry data from Denmark, Norway, and Sweden, we identified 3,183,316 children (born 1996-2018) and followed them from birth until leukemia diagnosis, censoring (death, emigration, other cancer, 20th birthday) or study closure (December 31st, 2017, 2018 or 2020). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for childhood leukemia (any, lymphoid and non-lymphoid) associated with maternal recent use (≤3 months before or during pregnancy) or previous use (before recent use) of hormonal contraception overall and by type, compared to no use. During 29,455,528 person-years, 1701 children developed leukemia (no use: 518, previous use: 974, recent use: 209). Maternal recent use of hormonal contraception was associated with an increased leukemia risk in children (HR 1.22, 95%CI 1.04-1.44; incidence rate per 1,000,000 person-years [IR] 65), compared to no use (IR 53). The association was strongest for non-lymphoid leukemia (HR 1.69, 95%CI 1.20-2.37) and mainly driven by the oral combined products, both for any leukemia (HR 1.29, 95%CI 1.05-1.59) and non-lymphoid leukemia (HR 1.75, 95%CI 1.17-2.62). Additionally, non-lymphoid leukemia was associated with recent use of the non-oral progestin-only products (HR 2.10, 95%CI 1.28-3.44). Although the absolute risk was low, maternal hormonal contraception use up to or during pregnancy was associated with an increased childhood leukemia risk, particularly non-lymphoid leukemia, and mainly driven by oral combined and non-oral progestin-only products.

Methionine Synthase Reductase A66G Variant in Pediatric Acute Lymphoblastic Leukemia Patients.

Methionine synthase reductase, which is encoded by the methionine synthase reductase (MTRR) gene, plays a crucial role in the methylation reactions and the production of DNA and its epigenetic processes. There was a correlation between the MTRR (A66G) polymorphism and the likelihood of developing acute lymphoblastic leukemia (ALL). This study was carried out to investigate the correlation among pediatric ALL cases. Within the participant population of this case-control study, there were 86 individuals who had been diagnosed with ALL, and there were also 150 healthy persons who acted as the control group. To determine the MTRR (A66G) polymorphism, DNA was first extracted and then observed through the use of real-time polymerase chain reaction. The results of the flow cytometry analysis showed that the prevalence of B-cell ALL (B-ALL) was much higher than that of T-cell ALL (T-ALL), which accounted for only 20 cases (23.3%). Upon comparing the hematological parameters of ALL subtypes in patients with T-ALL, it was discovered that there was a statistically significant higher mean total white blood count (P < 0.0005) and mean blast percentage (P = 0.050). Upon examination, it was discovered that both of these figures were much higher than the average. In accordance with the results of the molecular analysis, the occurrence of the MTRR homozygous GG genotype was found to be considerably lower in the patients' group (4.65%) than in the control group (20.67%). However, the MTRR homozygous AA and heterozygous AG were nearly similar in the two groups. The risk of acute lymphoblastic leukemia and MTRR genotypes, on the other hand, exhibited a correlation that was not statistically significant (P = 0.082). The study's findings showed that among pediatric ALL patients, the MTRR A66G polymorphism was not linked to an increased risk of ALL.

Molecular Secrets Revealed: How Diabetes may be Paving the Way for Leukemia.

Type 2 Diabetes Mellitus (T2DM) and leukemia are two major global health concerns, both contributing significantly to morbidity and mortality. Epidemiological evidence demonstrates a strong correlation between T2DM and an increased risk of leukemia, particularly driven by insulin resistance, hyperglycemia, and the resultant metabolic dysregulation. Key shared risk factors, including obesity and chronic inflammation, create a conducive environment for leukemogenesis, intensifying cancer cell proliferation and resistance to standard therapies. Insulin resistance, in particular, triggers oncogenic pathways such as PI3K/AKT and MAPK, exacerbating the aggressive phenotype seen in leukemia patients with T2DM. Additionally, clonal hematopoiesis of indeterminate potential (CHIP) is implicated in the higher leukemia risk observed in diabetic populations, especially among the elderly. Molecular mechanisms like the insulin-like growth factor (IGF) system further highlight the intricate link between these diseases, promoting survival and proliferation of leukemia cells. The coexistence of T2DM in leukemia patients is associated with poorer prognostic outcomes, including increased susceptibility to infections, reduced survival, and greater treatment resistance. Antidiabetic agents, notably metformin and pioglitazone, show promise in enhancing chemotherapy efficacy and improving patient outcomes by targeting metabolic pathways. These results highlight the need for comprehensive treatment approaches that target both metabolic abnormalities and cancer-related mechanisms in patients suffering from both T2DM and leukemia.

Identification of a Novel RUNX1::STX2 Fusion in Mixed-Phenotype Acute Leukemia (MPAL) With BCR::ABL1.

Mixed phenotype acute leukemia (MPAL) is a rare type of acute leukemia (AL), MPAL with BCR::ABL1 fusion is the main subtype of MPAL, mainly affecting adult males. It is an acute leukemia with unique clinical and biological characteristics that involve both the myeloid and lymphatic systems. Gene fusion plays a crucial role in the pathogenesis, diagnosis, prognosis assessment, and treatment of leukemia. We present the first discovery of a novel fusion of RUNX1::STX2 in this subtype, which is co-expressed with BCR::ABL1 fusion. RUNX1 is a crucial transcription factor for hematopoietic differentiation, frequently found to be abnormal in AML, while STX2 may play a role in cancer progression. The RUNX1::STX2 fusion protein may act as the primary negative regulator of wild-type RUNX1, influencing normal cell differentiation and proliferation, consequently elevating the risk of leukemia. The gene fusion status of this patient is unique and complex, requiring further exploration to understand its functional significance in leukemia progression and treatment response.

The Influence of DNA Repair Genes and Prenatal Tobacco Exposure on Risk of Childhood Acute Lymphoblastic Leukemia: A Gene-Environment Interaction Study.

Acute lymphoblastic leukemia (ALL) is the most common type of cancer among children. Tobacco exposure during gestation has been investigated as a potential risk factor, but its role remains undefined. Given tobacco's toxicologic profile as a DNA-damaging agent, we examined the impact of DNA repair gene variability as a source of vulnerability to tobacco exposure risk for ALL. Leveraging demographic and genotype data from two large California-based ALL epidemiology studies, we used logistic regression, MinimumP (minP) statistical method, and permutation tests to examine interactions between DNA repair genes and prenatal tobacco exposure. We found statistically significant interactions between prenatal tobacco exposure and DNA repair genes RECQL (minP = 1.00 × 10-4, FDR-P value = 1.86 × 10-2) and TDG (minP = 1.00 × 10-4, FDR-P value = 1.86 × 10-2) with regard to childhood ALL risk. Notable interactions in the homologous recombination pathway were observed among Latino children, whereas non-Latino White children displayed significant interactions in the base excision repair and nucleotide excision repair pathways. Our study highlights the significance of DNA repair genes and pathways when evaluating environmental exposure to tobacco smoke, suggesting that genetic variability within these pathways could impact vulnerability in the development of childhood ALL. This study highlights the significant impact of genetic variation interacting with prenatal tobacco exposure on ALL risk. Further research is needed to understand these interactions and their implications for ALL etiology. Expanding studies to other gene-environment interactions will aid in developing targeted prevention, diagnosis, and treatment strategies for pediatric oncology.

Causal effects of vitamin D on leukemia risk: insights from two-sample Mendelian randomization analysis.

vitamin D plays a crucial role in immune regulation, anti-inflammatory processes, and tumor suppression, but its relationship with leukemia risk remains unclear. This study aims to evaluate the causal relationship between vitamin D levels and the risk of different types of leukemia through a two-sample Mendelian randomization (MR) analysis. data from large-scale genome-wide association studies (GWAS) were used, and genetic variants associated with vitamin D were selected as instrumental variables. The relationship between vitamin D levels and the risk of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML) was examined. The inverse variance weighted (IVW) method was applied as the primary analytical approach. Heterogeneity was assessed through Cochran's Q test, pleiotropy was evaluated using the MR-Egger intercept, and sensitivity analyses were performed to ensure the robustness of the results. MR analysis showed a significant inverse association between serum 25-hydroxyvitamin D levels and the risk of CML (OR = 0.44, 95 % CI: 0.25-0.78, p = 0.005), suggesting a potential protective effect of vitamin D against CML. No significant causal relationships were found between vitamin D levels and the risks of AML, ALL, or CLL. Sensitivity analyses supported the robustness of these findings, with no evidence of heterogeneity or pleiotropy. the findings indicate that higher vitamin D levels may reduce the risk of CML, while the effects on other types of leukemia require further investigation. The potential role of vitamin D in leukemia prevention warrants more mechanistic studies and clinical validation.

Molecular Analysis of Genes CEBPA, NPM1, IDH1, and RUNX1 Polymorphisms as Biomarker Potential in Leukemia Patients.

Leukemia is found in approximately 2.3 million people worldwide and causes many deaths all over the world. This research study was conducted to figure out the link of single nucleotide polymorphisms of genes CEBPA (rs34529039), NPM1 (rs753788683), IDH1 (of rs11554137) and RUNX1 (rs13051066) polymorphisms as biomarker potential in leukemia patients. A total of 600 subjects were included in the study which included 300 patients and 300 healthy controls with age and gender matched. After DNA extraction, PCR was carried out to analyze polymorphisms of selected genes. A significant association with increased risk of leukemia by almost twofolds is observed in homozygous mutant (AA) of rs34529039 SNP of gene CEBPA (odds ratio [OR] = 1.71; 95% confidence interval [CI] = 1.04-2.82; p = 0.03) while highly significant association but with decrease risk of leukemia is observed in heterozygote genotype (CA) of same SNP (OR = 0.36; 95% CI = 0.22-0.59; p = 0.0001). A highly significant association with increased risk of leukemia up to twofolds is observed in heterozygote genotype (AG) of rs753788683 of gene NPM1 (OR 2.10: 95% CI 1.32-3.36 p = 0.0017) while increasing risk by two-fold and show significant association in homozygous mutant (AA) (OR = 1.75; 95% Cl = 1.09-2.79; p = 0.01). Leukemia risk increases by twofold and shows significant association in the homozygous mutant (AA) of rs11554137 (OR = 1.75; 95%Cl = 1.09-2.79; p = 0.01). Leukemia risk increases by twofold and shows significant association in the homozygous mutant (AA) of rs13051066 of gene RUNX1 (OR = 0.63; 95%Cl = 0.39-1.63; p = 0.06).

Indoor radon exposure: A systematic review of radon-induced health risks and evidence quality using GRADE approach

BackgroundRadon (Rn) is a radioactive gas with well-established carcinogenic properties. It is a significant contributor to natural background ionizing radiation exposure, accounting for over 50 % of human exposure. Prolonged exposure to radon gas has been conclusively linked to various health issues such as lung cancer, leukemia, and Chronic Obstructive Pulmonary Diseases (COPD). Despite this, there is a scarcity of comprehensive studies examining the quality of evidence establishing an association between indoor radon exposure and these health problems. ObjectiveWe performed a systematic review of peer-reviewed research articles to explore the current evidence on the potential association between residential radon exposure and human health, specifically focusing on lung cancer, COPD, and leukemia. MethodsA comprehensive search was conducted on PubMed and Google Scholar using MeSH terms and keywords (residential radon, radon AND lung cancer, radon AND COPD, radon AND leukemia). The inclusion criteria focused on studies that analyzed the link between residential radon exposure and lung cancer, leukemia and COPD. We searched for peer-reviewed studies published from 2010 to 2024. Studies carried out in occupational settings were not considered. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework to select relevant studies. Reviewers independently collected data, resolving disagreements through discussion. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate evidence quality, and the study was registered with PROSPERO, CRD42024550735. ResultsThe evidence indicating an associative or causal link between indoor radon and lung cancer was found to be of high quality or conclusive, particularly with stronger support from case-control studies. The findings for COPD and leukemia were inconclusive, indicating that additional research is necessary to establish a definitive link between residential radon exposure and these health outcomes. These associations was deemed moderate or inconclusive primarily due to methodological shortcomings, conflicting findings and the prevalence of weak study designs and poor exposure data. The existing evidence on the potential connection between residential radon exposure and the risk of COPD and leukemia is currently limited. In order to definitively confirm or disprove this association, more studies are needed. Further research is crucial to elucidate these relationships and to guide the development of effective public health interventions. ConclusionThe review found that the association between radon exposure and lung cancer was consistent with existing scientific knowledge. However, the evidence for association between indoor radon exposure and COPD was inconclusive. Additionally, evidence linking indoor radon exposure to leukemia was uncertain. Future research should use more robust study designs (cohort and case control studies) and directly measure long-term radon levels to investigate the potential association between residential radon exposure and COPD and leukemia.

APEX1 Polymorphisms Affect Acute Myeloid Leukemia Risk, and Its Expression Is Involved in Cell Proliferation and Differentiation.

The link between DNA repair gene polymorphisms and cancer susceptibility has gained significant attention. Thus, we investigated the impact of base excision repair (BER) gene polymorphisms on acute myeloid leukemia (AML) risk and pathogenesis. In total, 106 patients with AML and 191 healthy controls were included in the study, wherein polymorphisms in four BER genes (APEX1, MUTYH, OGG1, and XRCC1) were examined. Notably, the APEX1-656 T>G polymorphism exhibited a significant association with AML risk in the recessive (TT vs. TG + GG) (p = 0.046) and co-dominant models (TT vs. GG) (p = 0.02). Assessing APEX1 expression levels, APEX1 expression was elevated in the bone marrow of patients with AML compared with that in controls (p = 0.02). Subsequently, we compared the percentages of CD34+ cells between the APEX1 high or low expression groups, revealing a significant difference (high vs. low = 29.9% vs. 11.5%, p = 0.01). Additionally, we observed reduced APEX1 expression in HL60 cells differentiated with all-trans retinoic acid (p < 0.001). We hypothesized that APEX1 expression could correlate with stemness and analyzed its expression in stem and differentiated cells. In the GSE48558 dataset, AML cells and normal CD34+ cells expressed APEX1 at higher levels than did granulocytes (p < 0.01). Functional experiments revealed that APEX1 knockdown led to a reduction in AML cell proliferation. These findings indicated that APEX1 polymorphisms were a potential risk factor for AML and highlighted the important role of APEX1 in regulating AML cell differentiation and proliferation.