-
Frontiers in Oncology 2024Early-onset colorectal cancer (CRC), defined as diagnosis before age 50, has increased in recent decades. Although more often diagnosed at advanced stage, associations...
BACKGROUND
Early-onset colorectal cancer (CRC), defined as diagnosis before age 50, has increased in recent decades. Although more often diagnosed at advanced stage, associations with other histological and molecular markers that impact prognosis and treatment remain to be clarified. We conducted a systematic review and meta-analysis concerning the prevalence of prognostic and predictive tumor markers for early- vs. late-onset CRC, including oncogene mutations, microsatellite instability (MSI), and emerging markers including immune cells and the consensus molecular subtypes.
METHODS
We systematically searched PubMed for original research articles published between April 2013-January 2024. Included studies compared the prevalence of tumor markers in early- vs. late-onset CRC. A meta-analysis was completed and summary odds ratios (ORs) with 95% confidence intervals (CIs) were obtained from a random effects model via inverse variance weighting. A sensitivity analysis was completed to restrict the meta-analysis to studies that excluded individuals with Lynch syndrome, a hereditary condition that influences the distribution of tumor markers for early-onset CRC.
RESULTS
In total, 149 articles were identified. Tumors from early-onset CRC are less likely to include mutations in (OR, 95% CI: 0.91, 0.85-0.98), (0.63, 0.51-0.78), (0.70, 0.58-0.84), and (0.88, 0.78-1.00) but more likely to include mutations in (1.68, 1.04-2.73) and (1.34, 1.24-1.45). After limiting to studies that excluded Lynch syndrome, the associations between early-onset CRC and (0.77, 0.64-0.92) and mutation (0.81, 0.67-0.97) were attenuated, while an inverse association with mutation was also observed (0.88, 0.78-0.99). Early-onset tumors are less likely to develop along the CpG Island Methylator Phenotype pathway (0.24, 0.10-0.57), but more likely to possess adverse histological features including high tumor grade (1.20, 1.15-1.25), and mucinous (1.22, 1.16-1.27) or signet ring histology (2.32, 2.08-2.57). A positive association with MSI status (1.31, 1.11-1.56) was also identified. Associations with immune markers and the consensus molecular subtypes are inconsistent.
DISCUSSION
A lower prevalence of mutations in and is consistent with extended survival and superior response to targeted therapies for metastatic disease. Conversely, early-onset CRC is associated with aggressive histological subtypes and and mutations, which may serve as therapeutic targets.
PubMed: 38737895
DOI: 10.3389/fonc.2024.1349572 -
Radiotherapy and Oncology : Journal of... Jul 2024We performed this systematic review and meta-analysis to investigate the performance of ML in detecting genetic mutation status in NSCLC patients. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
We performed this systematic review and meta-analysis to investigate the performance of ML in detecting genetic mutation status in NSCLC patients.
MATERIALS AND METHODS
We conducted a systematic search of PubMed, Cochrane, Embase, and Web of Science up until July 2023. We discussed the genetic mutation status of EGFR, ALK, KRAS, and BRAF, as well as the mutation status at different sites of EGFR.
RESULTS
We included a total of 128 original studies, of which 114 constructed ML models based on radiomic features mainly extracted from CT, MRI, and PET-CT data. From a genetic mutation perspective, 121 studies focused on EGFR mutation status analysis. In the validation set, for the detection of EGFR mutation status, the aggregated c-index was 0.760 (95%CI: 0.706-0.814) for clinical feature-based models, 0.772 (95%CI: 0.753-0.791) for CT-based radiomics models, 0.816 (95%CI: 0.776-0.856) for MRI-based radiomics models, and 0.750 (95%CI: 0.712-0.789) for PET-CT-based radiomics models. When combined with clinical features, the aggregated c-index was 0.807 (95%CI: 0.781-0.832) for CT-based radiomics models, 0.806 (95%CI: 0.773-0.839) for MRI-based radiomics models, and 0.822 (95%CI: 0.789-0.854) for PET-CT-based radiomics models. In the validation set, the aggregated c-indexes for radiomics-based models to detect mutation status of ALK and KRAS, as well as the mutation status at different sites of EGFR were all greater than 0.7.
CONCLUSION
The use of radiomics-based methods for early discrimination of EGFR mutation status in NSCLC demonstrates relatively high accuracy. However, the influence of clinical variables cannot be overlooked in this process. In addition, future studies should also pay attention to the accuracy of radiomics in identifying mutation status of other genes in EGFR.
Topics: Humans; Lung Neoplasms; Machine Learning; Mutation; Carcinoma, Non-Small-Cell Lung; Positron Emission Tomography Computed Tomography; ErbB Receptors; Proto-Oncogene Proteins p21(ras)
PubMed: 38734145
DOI: 10.1016/j.radonc.2024.110325 -
Cureus Apr 2024The oncogenic potential of human papillomavirus (HPV) has been widely acknowledged in relation to multiple types of cancer. The objective of this investigation was to... (Review)
Review
The oncogenic potential of human papillomavirus (HPV) has been widely acknowledged in relation to multiple types of cancer. The objective of this investigation was to conduct a comprehensive assessment of the available evidence pertaining to the correlation between HPV and various types of cancer, such as cervical, colon, ovarian, and head and neck cancers, in the Kingdom of Saudi Arabia (KSA). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were complied with to conduct a systematic literature search aimed at identifying studies that explore the correlation between HPV and the specified cancers. Databases such as Web of Science, Embase, PubMed, and the Cochrane Library were queried up until May of 2023. Relevant literature was obtained, information was extracted, and the methodological rigor was evaluated. The high-risk HPV, namely HPV-16 and HPV-18, were detected as the most prevalent variants in KSA. A significant proportion of cervical cancer cases in the region were found to be associated HPV infection. The molecular tests have furnished evidence that establishes a connection between HPV infection and colonic polyps as well as colorectal cancer. This finding suggests that HPV may have a plausible role in the etiology of these medical conditions. The results of genotyping and integration analyses suggest a probable correlation between HPV and the development of ovarian cancer. Additionally, the prevalence of head and neck squamous cell cancer related to HPV was notably reduced in this particular geographical area. This study presents persuasive findings that establish a connection between HPV and cervical cancer and proposes plausible correlations with squamous cell carcinomas in the colon, ovaries, and head and neck. The aforementioned results emphasize the necessity for additional inquiry into the function of HPV in the onset and advancement of said malignancies. Further investigations are necessary to augment our comprehension of the role of HPV in these neoplasms.
PubMed: 38721199
DOI: 10.7759/cureus.57851 -
Frontiers in Public Health 2024During the use of electronic cigarettes (e-cigarettes), users are still exposed to carcinogens similar to those found in tobacco products. Since these carcinogens are... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
During the use of electronic cigarettes (e-cigarettes), users are still exposed to carcinogens similar to those found in tobacco products. Since these carcinogens are metabolized and excreted in urine, they may have carcinogenic effects on the bladder urinary tract epithelium. This meta-analysis aimed to compare bladder cancer carcinogens in the urine of tobacco users and e-cigarette users using a large number of samples.
METHODS
A systematic meta-analysis was performed using data obtained from several scientific databases (up to November 2023). This cumulative analysis was performed following the Preferred Reporting Items for Systematic Evaluation and Meta-Analysis (PRISMA) and Assessing the Methodological Quality of Systematic Evaluations (AMSTAR) guidelines, according to a protocol registered with PROSPERO. This study was registered on PROSPERO and obtained the unique number: CRD42023455600.
RESULTS
The analysis included 10 high-quality studies that considered polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs) and tobacco-specific nitrosamines (TSNAs). Statistical indicators show that there is a difference between the tobacco user group and the e-cigarette user group in terms of 1-Hydroxynaphthalene (1-NAP) [weighted mean difference (WMD)10.14, 95% confidence interval (CI) (8.41 to 11.88), < 0.05], 1-Hydroxyphenanthrene (1-PHE) [WMD 0.08, 95% CI (-0.14 to 0.31), > 0.05], 1-Hydroxypyrene (1-PYR) [WMD 0.16, 95% CI (0.12 to 0.20), < 0.05], 2-Hydroxyfluorene (2-FLU) [WMD 0.69, 95% CI (0.58 to 0.80), < 0.05], 2-Hydroxynaphthalene (2-NAP) [WMD 7.48, 95% CI (4.15 to 10.80), < 0.05], 3-Hydroxyfluorene (3-FLU) [WMD 0.57, 95% CI (0.48 to 0.66), < 0.05], 2-Carbamoylethylmercapturic acid (AAMA) [WMD 66.47, 95% CI (27.49 to 105.46), < 0.05], 4-Hydroxy-2-buten-1-yl-mercapturic acid (MHBMA) [WMD 287.79, 95% CI (-54.47 to 630.04), > 0.05], 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNAL) [WMD 189.37, 95% CI (78.45 to 300.29), < 0.05], or N0-nitrosonornicotine (NNN) [WMD 11.66, 95% CI (7.32 to 16.00), < 0.05].
CONCLUSION
Urinary bladder cancer markers were significantly higher in traditional tobacco users than in e-cigarette users.: PROSPERO (CRD42023455600: https://www.crd.york.ac.uk/PROSPERO/).
Topics: Humans; Urinary Bladder Neoplasms; Electronic Nicotine Delivery Systems; Carcinogens; Volatile Organic Compounds; Carcinogenesis; Polycyclic Aromatic Hydrocarbons; Biomarkers; Nitrosamines; Tobacco Products
PubMed: 38716244
DOI: 10.3389/fpubh.2024.1385628 -
Wiley Interdisciplinary Reviews. RNA 2024Long noncoding RNAs (lncRNA) are a class of non-coding RNAs greater than 200 bp in length with limited peptide-coding function. The transcription of LINC00152 is... (Review)
Review
Long noncoding RNAs (lncRNA) are a class of non-coding RNAs greater than 200 bp in length with limited peptide-coding function. The transcription of LINC00152 is derived from chromosome 2p11.2. Many studies prove that LINC00152 influences the progression of various tumors via promoting the tumor cells malignant phenotype, chemoresistance, and immune escape. LINC00152 is regulated by multiple transcription factors and DNA hypomethylation. In addition, LINC00152 participates in the regulation of complex molecular signaling networks through epigenetic regulation, protein interactions, and competitive endogenous RNA (ceRNA). Here, we provide a systematic review of the upstream regulatory factors of LINC00152 expression level in different types of tumors. In addition, we revisit the main functions and mechanisms of LINC00152 as driver oncogene and biomarker in pan-cancer. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Methods > RNA Analyses in Cells RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.
Topics: RNA, Long Noncoding; Humans; Neoplasms; Oncogenes; Gene Expression Regulation, Neoplastic
PubMed: 38702938
DOI: 10.1002/wrna.1851 -
Journal of Clinical Pathology Jun 2024A mutation in the gene which encodes BRG1, a common catalytic subunit of switch/sucrose non-fermentable chromatin-remodelling complexes, plays a vital role in... (Meta-Analysis)
Meta-Analysis
AIMS
A mutation in the gene which encodes BRG1, a common catalytic subunit of switch/sucrose non-fermentable chromatin-remodelling complexes, plays a vital role in carcinogenesis. mutations are present in approximately 10% of non-small cell lung cancers (NSCLC), making it a crucial gene in NSCLC, but with varying prognostic associations. To explore this, we conducted a systematic review and meta-analysis on the prognostic significance of mutations in NSCLC.
METHODS
Electronic database search was performed from inception to December 2022. Study characteristics and prognostic data were extracted from each eligible study. Depending on heterogeneity, pooled HR and 95% CI were derived using the random-effects or fixed-effects models.
RESULTS
8 studies (11 cohorts) enrolling 8371 patients were eligible for inclusion. Data on overall survival (OS) and progression-free survival (PFS) were available from 8 (10 cohorts) and 1 (3 cohorts) studies, respectively. Comparing -mutated NSCLC patients with -wild-type NSCLC patients, the summary HRs for OS and PFS were 1.49 (95% CI 1.18 to 1.87; I=84%) and 3.97 (95% CI 1.32 to 11.92; I=79%), respectively. The results from the trim-and-fill method for publication bias and sensitivity analysis were inconsistent with the primary analyses. Three studies reported NSCLC prognosis for category I and II mutations separately; category I was significantly associated with OS.
CONCLUSION
Our findings suggest that mutation negatively affects NSCLC OS and PFS. The prognostic effects of -co-occurring mutations and the predictive role of mutation status in immunotherapy require further exploration.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; DNA Helicases; Transcription Factors; Nuclear Proteins; Mutation; Prognosis; Biomarkers, Tumor
PubMed: 38702192
DOI: 10.1136/jcp-2024-209394 -
The Cochrane Database of Systematic... May 2024Asbestos exposure can lead to asbestos-related diseases. The European Union (EU) has adopted regulations for workplaces where asbestos is present. The EU occupational... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Asbestos exposure can lead to asbestos-related diseases. The European Union (EU) has adopted regulations for workplaces where asbestos is present. The EU occupational exposure limit (OEL) for asbestos is 0.1 fibres per cubic centimetre of air (f/cm) as an eight-hour average. Different types of personal protective equipment (PPE) are available to provide protection and minimise exposure; however, their effectiveness is unclear.
OBJECTIVES
To assess the effects of personal protective equipment (PPE), including donning and doffing procedures and individual hygienic behaviour, compared to no availability and use of such equipment or alternative equipment, on asbestos exposure in workers in asbestos demolition and repair work.
SEARCH METHODS
We searched MEDLINE, Embase, CENTRAL, and Scopus (September 2022), and we checked the reference lists of included studies.
SELECTION CRITERIA
We included studies that measured asbestos concentration outside and inside PPE (considering outside concentration a surrogate for no PPE), exposure to asbestos after doffing PPE, donning and doffing errors, nonadherence to regulations, and adverse effects of PPE.
DATA COLLECTION AND ANALYSIS
Two review authors selected studies, extracted data, and assessed risk of bias using ROBINS-I. We categorised PPE as full-face filtering masks, supplied air respirators (SARs), and powered air-purifying respirators (PAPRs). Values for asbestos outside and inside PPE were transformed to logarithmic values for random-effects meta-analysis. Pooled logarithmic mean differences (MDs) were exponentiated to obtain the ratio of means (RoM) and 95% confidence interval (95% CI). The RoM shows the degree of protection provided by the respirators (workplace protection factor). Since the RoM is likely to be much higher at higher outside concentrations, we presented separate results according to the outside asbestos concentration, as follows. • Below 0.01 f/cm (band 1) • 0.01 f/cm to below 0.1 f/cm (band 2) • 0.1 f/cm to below 1 f/cm (band 3) • 1 f/cm to below 10 f/cm (band 4) • 10 f/cm to below 100 f/cm (band 5) • 100 f/cm to below 1000 f/cm (band 6) Additionally, we determined whether the inside concentrations per respirator and concentration band complied with the current EU OEL (0.1 f/cm) and proposed EU OEL (0.01 f/cm).
MAIN RESULTS
We identified six studies that measured asbestos concentrations outside and inside respiratory protective equipment (RPE) and one cross-over study that compared the effect of two different coveralls on body temperature. No studies evaluated the remaining predefined outcomes. Most studies were at overall moderate risk of bias due to insufficient reporting. The cross-over study was at high risk of bias. Full-face filtering masks Two studies evaluated full-face filtering masks. They provided insufficient data for band 1 and band 6. The results for the remaining bands were as follows. • Band 2: RoM 19 (95% CI 17.6 to 20.1; 1 study, 3 measurements; moderate certainty) • Band 3: RoM 69 (95% CI 26.6 to 175.9; 2 studies, 17 measurements; very low certainty) • Band 4: RoM 455 (95% CI 270.4 to 765.1; 1 study, 16 measurements; low certainty) • Band 5: RoM 2752 (95% CI 1236.5 to 6063.2;1 study, 3 measurements; low certainty) The inside measurements in band 5 did not comply with the EU OEL of 0.1 f/cm, and no inside measurements complied with the proposed EU OEL of 0.01 f/cm. Supplied air respirators Two studies evaluated supplied air respirators. They provided no data for band 6. The results for the remaining bands were as follows. • Band 1: RoM 11 (95% CI 7.6 to 14.9; 1 study, 134 measurements; moderate certainty) • Band 2: RoM 63 (95% CI 43.8 to 90.9; 1 study, 17 measurements; moderate certainty) • Band 3: RoM 528 (95% CI 368.7 to 757.5; 1 study, 38 measurements; moderate certainty) • Band 4: RoM 4638 (95% CI 3071.7 to 7044.5; 1 study, 49 measurements; moderate certainty) • Band 5: RoM 26,134 (16,647.2 to 41,357.1; 1 study, 22 measurements; moderate certainty) All inside measurements complied with the current OEL of 0.1 f/cm and the proposed OEL of 0.01 f/cm. Powered air-purifying respirators Three studies evaluated PAPRs. The results per band were as follows. • Band 1: RoM 8 (95% CI 3.7 to 19.1; 1 study, 23 measurements; moderate certainty) • Band 2: RoM 90 (95% CI 64.7 to 126.5; 1 study, 17 measurements; moderate certainty) • Band 3: RoM 104 (95% CI 23.1 to 464.1; 3 studies, 14 measurements; very low certainty) • Band 4: RoM 706 (95% CI 219.2 to 2253.0; 2 studies, 43 measurements; very low certainty) • Band 5: RoM 1366 (544.6 to 3428.9; 2 studies, 8 measurements; low certainty) • Band 6: RoM 18,958 (95% CI 4023.9 to 90,219.4; 2 studies, 13 measurements; very low certainty) All inside measurements complied with the 0.1 f/cm OEL when the outside concentration was below 10 f/cm (band 1 to band 4). From band 3, no measurements complied with the proposed OEL of 0.01 f/cm. Different types of coveralls One study reported the adverse effects of coveralls. A polyethylene suit may increase the body temperature more than a ventilated impermeable polyvinyl (PVC) coverall, but the evidence is very uncertain (MD 0.17 °C, 95% CI -0.08 to 0.42; 1 study, 11 participants; very low certainty).
AUTHORS' CONCLUSIONS
Where the outside asbestos concentration is below 0.1 f/cm, SARS and PAPRs likely reduce exposure to below the proposed OEL of 0.01 f/cm. For outside concentrations up to 10 f/cm, all respirators may reduce exposure below the current OEL, but only SAR also below the proposed OEL. In band 5 (10 to < 100 f/cm), full-face filtering masks may not reduce asbestos exposure below either OEL, SARs likely reduce exposure below both OELs, and there were no data for PAPRs. In band 6 (100 f/cm to < 1000 f/cm), PAPRs may not reduce exposure below either OEL, and there were no data for full-face filtering masks or SARs. Some coveralls may increase body temperature more than others. Randomised studies are needed to directly compare PAPRs and SARs at higher asbestos concentrations and to assess adverse effects. Future studies should assess the effects of doffing procedures.
Topics: Humans; Asbestos; Bias; Masks; Occupational Exposure; Personal Protective Equipment; Respiratory Protective Devices
PubMed: 38695617
DOI: 10.1002/14651858.CD015158.pub2 -
Toxics Apr 2024Biomonitoring of human populations exposed to chemical substances that can act as potential mutagens or carcinogens, may enable the detection of damage and early disease... (Review)
Review
Biomonitoring of human populations exposed to chemical substances that can act as potential mutagens or carcinogens, may enable the detection of damage and early disease prevention. In recent years, the comet assay has become an important tool for assessing DNA damage, both in environmental and occupational exposure contexts. To evidence the role of the comet assay in human biomonitoring, we have analysed original research studies of environmental or occupational exposure that used the comet assay in their assessments, following the PRISMA-ScR method (preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews). Groups of chemicals were designated according to a broad classification, and the results obtained from over 300 original studies (n = 123 on air pollutants, n = 14 on anaesthetics, n = 18 on antineoplastic drugs, n = 57 on heavy metals, n = 59 on pesticides, and n = 49 on solvents) showed overall higher values of DNA strand breaks in the exposed subjects in comparison with the unexposed. In summary, our systematic scoping review strengthens the relevance of the use of the comet assay in assessing DNA damage in human biomonitoring studies.
PubMed: 38668493
DOI: 10.3390/toxics12040270 -
Medical Oncology (Northwood, London,... Apr 2024Myeloid neoplasms are a group of bone marrow diseases distinguished by disruptions in the molecular pathways that regulate the balance between hematopoietic stem cell... (Review)
Review
Myeloid neoplasms are a group of bone marrow diseases distinguished by disruptions in the molecular pathways that regulate the balance between hematopoietic stem cell (HSC) self-renewal and the generation of specialized cells. Cytokines and chemokines, two important components of the inflammatory process, also influence hematological differentiation. In this scenario, immunological dysregulation plays a pivotal role in the pathogenesis of bone marrow neoplasms. The STING pathway recognizes DNA fragments in the cell cytoplasm and triggers an immune response by type I interferons. The role of STING in cancer has not yet been established; however, both actions, as an oncogene or tumor suppressor, have been documented in other types of cancer. Therefore, we performed a systematic review (registered in PROSPERO database #CRD42023407512) to discuss the role of STING pathway in the advancement of pathogenesis and/or prognosis for different myeloid neoplasms. In brief, scientific evidence supports investigations that primarily use cell lines from myeloid neoplasms, such as leukemia. More high-quality research and clinical trials are needed to understand the role of the STING pathway in the pathology of hematological malignancies. Finally, the STING pathway suggests being a promising therapeutic molecular target, particularly when combined with current drug therapies.
Topics: Humans; Hematologic Neoplasms; Membrane Proteins; Myeloproliferative Disorders; Signal Transduction
PubMed: 38656461
DOI: 10.1007/s12032-024-02376-8 -
Toxicology Jun 2024E-waste -the aftermath of large amount of electrical and electronic equipment ferried into Africa from which Nigeria receives a significant chunk, is composed of...
E-waste -the aftermath of large amount of electrical and electronic equipment ferried into Africa from which Nigeria receives a significant chunk, is composed of components known to be hazardous to health. Composition of series of heavy metals (HMs) in e-waste is traceable to many health conditions including cancer which is hitherto incompletely understood. This study harmonizes primary data on HMs from e-waste in different Nigerian environmental media including the air, soil, surface dust, water and plant. We estimated the possible health implications, single and aggregative soil and water pollution indices both in adult and children categories, carcinogenic and non-carcinogenic risks secondary to HM exposure and mapped out the possible mechanism of carcinogenesis. Analysis showed that soil, water, surface dust and plant matrices in Nigerian environment are variedly but considerably contaminated with combination of HMs. The significantly high values of the hazard quotient and hazard index of both water and surface dust matrices are indicative of adverse health effect of the non-carcinogenic risk. The highest HQ is generated by Pb and Cr through dermal exposure to soil and surface dust with mean values of 1718.48, 1146.14, 1362.10 and 1794.61 respectively among Nigerian children followed by the oral exposure. This pattern of observation is similar to that obtained for adult category. HI due to Pb and Cr in soil constitutes the highest HI (2.05E+03 and 1.18E+03 respectively) followed by surface dust. However, this study precipitates the observation that children are more at health risk than adults in contaminated environment. Carcinogenic risk also follows the same pattern of expression in the Nigerian environment. We conclude that exposure to e-waste poses significant carcinogenic and non-carcinogenic health risks and the induction of toxicity may be mediated via DNA damage, oxidative stress and inflammatory/immune cells dysfunction in Nigerian environment.
Topics: Humans; Carcinogens; Electronic Waste; Environmental Exposure; Environmental Monitoring; Environmental Pollutants; Metals, Heavy; Nigeria; Risk Assessment; Waste Management
PubMed: 38653375
DOI: 10.1016/j.tox.2024.153811