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The Journal of International Medical... Jan 2022Breast cancer (BC) is the most common form of cancer among Asian females. Mutations in the / genes are often observed in BC cases and largely increase the lifetime risk...
OBJECTIVE
Breast cancer (BC) is the most common form of cancer among Asian females. Mutations in the / genes are often observed in BC cases and largely increase the lifetime risk of having BC. Because of the paucity of high-quality data on the molecular spectrum of mutations in South Asian populations, we aimed to explore these mutations among South Asian countries.
METHODS
A systematic literature search was performed for the and gene mutation spectrum using electronic databases such as PubMed, EMBASE, and Google Scholar. Twenty studies were selected based on specific inclusion and exclusion criteria.
RESULTS
The 185delAG (c.68_69del) mutation in exon 2 of was the most common recurrent mutation and founder mutation found. Various intronic variants, variants of unknown significance, large genomic rearrangements, and polymorphisms were also described in some studies.
CONCLUSIONS
The South Asian population has a wide variety of genetic mutations of and that differ according to countries and ethnicities. A stronger knowledge of various population-specific mutations in these cancer susceptibility genes can help provide efficient strategies for genetic testing.
Topics: Asia; BRCA1 Protein; BRCA2 Protein; Breast Neoplasms; Female; Genes, BRCA2; Genetic Predisposition to Disease; Humans; Mutation; Neoplasm Recurrence, Local; Ovarian Neoplasms; Spectrum Analysis
PubMed: 35000471
DOI: 10.1177/03000605211070757 -
European Journal of Medical Research Aug 2023The aim of this study was to evaluate the efficacy and safety of osimertinib for the treatment of leptomeningeal metastases (LM) from epidermal growth factor receptor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this study was to evaluate the efficacy and safety of osimertinib for the treatment of leptomeningeal metastases (LM) from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC).
METHODS
We conducted a systematic review and meta-analysis to aggregate the clinical outcomes of patients with LM from EGFR-mutant NSCLC treated with osimertinib. A comprehensive literature search for published and unpublished studies was implemented in April 2021 of PubMed, EMBASE, the Cochrane Library, and several international conference databases, in accordance with the PRISMA guidelines. Meta-analysis of proportions was conducted to calculate the pooled rate of overall response rate (ORR), disease control rate (DCR), one-year overall survival (OS), and adverse events (AEs).
RESULTS
A total of eleven studies (five prospective and six retrospective) including 353 patients were included. The majority of patients (346/353, 98.0%) received osimertinib as ≥ 2nd-line treatment for LM, either at a dosage of 80 mg (161/353, 45.6%) or 160 mg (191/353, 54.1%). The pooled rates of ORR and DCR were 42% (95% CI 24% to 59%) and 93% (95% CI 88% to 97%), respectively. The pooled one-year OS rate was 59% (95% CI 53% to 65%) in 233 patients from five studies. The highest incidence of AEs of all grades was rash (53%), followed by diarrhea (45%), paronychia (35%), decreased appetite (35%), and dry skin (27%), based on data from four studies.
CONCLUSIONS
Our study highlighted and confirmed the meaningful efficacy and a manageable safety profile of osimertinib for the treatment of LM from EGFR-mutant advanced NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Retrospective Studies; Prospective Studies; Antineoplastic Agents; ErbB Receptors; Protein Kinase Inhibitors; Mutation
PubMed: 37542339
DOI: 10.1186/s40001-023-01219-y -
BMC Genomic Data Jan 2024In this study, we aim to investigate the association between BRCA1/2 mutation and uterine cancer incidence. (Meta-Analysis)
Meta-Analysis
PURPOSE
In this study, we aim to investigate the association between BRCA1/2 mutation and uterine cancer incidence.
MATERIAL AND METHOD
We systematically searched three databases including PubMed, Scopus, and Google Scholar up to August 2023; and reviewed 23 cohorts and cross-sectional studies to explore the association between BRCA1/2 mutations and uterine cancer incidence.
RESULTS
This systematic review comprised a total of 21 cohort studies and 2 cross-sectional studies after the screening process. According to meta-analysis the prevalence of the BRCA1/2 gene in patients with uterine cancer was 0.02 (95%CI = [0.01,0.03], P < 0.01, I = 94.82%) CONCLUSIONS: Our meta-analysis investigates a 2% prevalence of BRCA1/2 mutation in patients with uterine cancer. Patients with BRCA1/2 mutations might be more conscious of uterine malignancies.
Topics: Female; Humans; BRCA1 Protein; BRCA2 Protein; Cross-Sectional Studies; Mutation; Uterine Neoplasms
PubMed: 38297203
DOI: 10.1186/s12863-024-01189-y -
Neurogenetics Oct 2022C-terminal binding proteins (CtBP1/2) are transcriptional coregulators that play a significant role during vertebrate neurodevelopment. This systematic review aims to... (Review)
Review
C-terminal binding proteins (CtBP1/2) are transcriptional coregulators that play a significant role during vertebrate neurodevelopment. This systematic review aims to identify case reports with genetic variants in CTBP1 and CTBP2 associated with brain development syndromes.We screened different databases (PubMed, Scopus, Google Scholar, LILACS) by systematically searching journals and checking reference lists and citations of background papers. We found fourteen cases (10 males) from five papers carrying two pathogenic, heterozygous variants in the CTBP1 gene (13 individuals carried the missense mutation c.991C T, p.Arg342Trp, and one subject carrying the 2-base pair deletion c.1315_1316delCA, p.Gln439ValfsTer84). These mutations were de novo in 13 cases and one case of maternal germinal mosaicism. Two variants are in the same domain of the protein: Pro-Leu-Asp-Leu-Ser (PLDLS) C terminal. Patients with these mutations exhibit a phenotype with intellectual disability, HADDTS syndrome (hypotonia, ataxia, developmental delay, and tooth enamel defects), and cerebellar volume loss. We did not identify reported cases associated with homozygous mutations harbored in CTBP1. We did not identify any report of neurodevelopment phenotypes associated with heterozygous or homozygous CTBP2 mutations. Due to CTBP2/RIBEYE being a gene with dual function, identifying and interpreting the potential pathogenic variants is challenging.Further, homozygous mutations in the CTBP2 gene may be lethal. The mechanisms involved in the pathogenesis of neurodevelopment due to variants of these proteins have not yet been elucidated, despite some functional evidence. Further studies should be conducted to understand these transcription factors and their interaction with each other and their partners.
Topics: Humans; Alcohol Oxidoreductases; Ataxia; Co-Repressor Proteins; Muscle Hypotonia; Mutation; Mutation, Missense; Transcription Factors
PubMed: 36331689
DOI: 10.1007/s10048-022-00700-w -
Scientific Reports Aug 2016Mitochondrial functions are intrinsically linked to their morphology and membrane ultrastructure. Characterizing abnormal mitochondrial structural features may thus... (Review)
Review
Mitochondrial functions are intrinsically linked to their morphology and membrane ultrastructure. Characterizing abnormal mitochondrial structural features may thus provide insight into the underlying pathogenesis of inherited and acquired mitochondrial diseases. Following a systematic literature review on ultrastructural defects in mitochondrial myopathy, we investigated skeletal muscle biopsies from seven subjects with genetically defined mtDNA mutations. Mitochondrial ultrastructure and morphology were characterized using two complimentary approaches: transmission electron microscopy (TEM) and serial block face scanning EM (SBF-SEM) with 3D reconstruction. Six ultrastructural abnormalities were identified including i) paracrystalline inclusions, ii) linearization of cristae and abnormal angular features, iii) concentric layering of cristae membranes, iv) matrix compartmentalization, v) nanotunelling, and vi) donut-shaped mitochondria. In light of recent molecular advances in mitochondrial biology, these findings reveal novel aspects of mitochondrial ultrastructure and morphology in human tissues with implications for understanding the mechanisms linking mitochondrial dysfunction to disease.
Topics: Aged; Biopsy; DNA, Mitochondrial; Female; Humans; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Middle Aged; Mitochondria, Muscle; Mitochondrial Myopathies; Muscle, Skeletal; Mutation; Young Adult
PubMed: 27506553
DOI: 10.1038/srep30610 -
BMC Cancer Aug 2023Breast cancer susceptibility gene (BRCA) mutation carriers are at an increased risk for breast, ovarian, prostate and pancreatic cancers. However, the role of BRCA is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Breast cancer susceptibility gene (BRCA) mutation carriers are at an increased risk for breast, ovarian, prostate and pancreatic cancers. However, the role of BRCA is unclear in colorectal cancer; the results regarding the association between BRCA gene mutations and colorectal cancer risk are inconsistent and even controversial. This study aimed to investigate whether BRCA1 and BRCA2 gene mutations are associated with colorectal cancer risk.
METHODS
In this systematic review, we searched PubMed/MEDLINE, Embase and Cochrane Library databases, adhering to PRISMA guidelines. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). Unadjusted odds ratios (ORs) were used to estimate the probability of Breast Cancer Type 1 Susceptibility gene (BRCA1) and Breast Cancer Type 2 Susceptibility gene (BRCA2) mutations in colorectal cancer patients. The associations were evaluated using fixed effect models.
RESULTS
Fourteen studies were included in the systematic review. Twelve studies, including seven case-control and five cohort studies, were included in the meta-analysis. A significant increase in the frequency of BRCA1 and BRCA2 mutations was observed in patients with colorectal cancer [OR = 1.34, 95% confidence interval (CI) = 1.02-1.76, P = 0.04]. In subgroup analysis, colorectal cancer patients had an increased odds of BRCA1 (OR = 1.48, 95% CI = 1.10-2.01, P = 0.01) and BRCA2 (OR = 1.56, 95% CI = 1.06-2.30, P = 0.02) mutations.
CONCLUSIONS
BRCA genes are one of the genes that may increase the risk of developing colorectal cancer. Thus, BRCA genes could be potential candidates that may be included in the colorectal cancer genetic testing panel.
Topics: Male; Humans; Genes, Tumor Suppressor; Genetic Testing; Mutation; Colorectal Neoplasms; Breast Neoplasms
PubMed: 37644384
DOI: 10.1186/s12885-023-11328-w -
American Journal of Preventive Medicine Nov 2022A systematic literature review was conducted to determine whether physical activity levels during adolescent and young adult years were associated with a reduced...
INTRODUCTION
A systematic literature review was conducted to determine whether physical activity levels during adolescent and young adult years were associated with a reduced lifetime risk of breast cancer among carriers of deleterious mutations in BRCA1 and BRCA2 genes.
METHODS
Ovid/MEDLINE, Embase, CENTRAL, WOS, and CINAHL were searched for articles including information about adolescent and young adult physical activity and breast cancer incidence among women carrying deleterious BRCA1 and BRCA2 gene mutations (search was initiated in October 2019; last update and full analyses were in March 2021). Independent reviewers screened articles at the title/abstract and full-text levels, resolving differences by consensus with lead authors. The NIH Quality Assessment Tools were used to assess sources of bias.
RESULTS
A total of 1,957 unique articles were identified; 5 met inclusion criteria. Samples size ranged from 68 to 1,185. All studies relied on self-reported adolescent and young adult physical activity. One study measured sports involvement; the others measured recreational activity. One large study was null, whereas 4 others showed a reduction in breast cancer incidence later in life with higher adolescent and young adult physical activity (p≤0.05). However, the protection was limited to premenopausal breast cancer in 1 of the studies (OR=0.62; 95% CI=0.40, 0.96; p-trend=0.01). In addition, adolescent and young adult physical activity was associated with older age at breast cancer diagnosis in 1 study (p=0.03).
CONCLUSIONS
A limited number of studies suggest that adolescent and young adult physical activity may reduce or delay the risk of breast cancer incidence among carriers of deleterious mutations in BRCA1 and BRCA2 genes.
Topics: Young Adult; Adolescent; Female; Humans; Breast Neoplasms; Mutation; Genes, BRCA2; Heterozygote; Exercise
PubMed: 35738959
DOI: 10.1016/j.amepre.2022.04.022 -
La Radiologia Medica Feb 2023This study aimed to systematically summarize the performance of the machine learning-based radiomics models in the prediction of microsatellite instability (MSI) in... (Review)
Review
This study aimed to systematically summarize the performance of the machine learning-based radiomics models in the prediction of microsatellite instability (MSI) in patients with colorectal cancer (CRC). It was conducted according to the preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy studies (PRISMA-DTA) guideline and was registered at the PROSPERO website with an identifier CRD42022295787. Systematic literature searching was conducted in databases of PubMed, Embase, Web of Science, and Cochrane Library up to November 10, 2022. Research which applied radiomics analysis on preoperative CT/MRI/PET-CT images for predicting the MSI status in CRC patients with no history of anti-tumor therapies was eligible. The radiomics quality score (RQS) and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) were applied to evaluate the research quality (full score 100%). Twelve studies with 4,320 patients were included. All studies were retrospective, and only four had an external validation cohort. The median incidence of MSI was 19% (range 8-34%). The area under the receiver operator curve of the models ranged from 0.78 to 0.96 (median 0.83) in the external validation cohort. The median sensitivity was 0.76 (range 0.32-1.00), and the median specificity was 0.87 (range 0.69-1.00). The median RQS score was 38% (range 14-50%), and half of the studies showed high risk in patient selection as evaluated by QUADAS-2. In conclusion, while radiomics based on pretreatment imaging modalities had a high performance in the prediction of MSI status in CRC, so far it does not appear to be ready for clinical use due to insufficient methodological quality.
Topics: Humans; Colorectal Neoplasms; Machine Learning; Microsatellite Instability; Positron Emission Tomography Computed Tomography; Retrospective Studies
PubMed: 36648615
DOI: 10.1007/s11547-023-01593-x -
Gynecologic Oncology Mar 2024POLE mutated endometrial carcinomas may represent a subspecific type of tumors harboring a more favorable prognosis. Grade 3 (G3 or high-grade) endometrioid endometrial... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
POLE mutated endometrial carcinomas may represent a subspecific type of tumors harboring a more favorable prognosis. Grade 3 (G3 or high-grade) endometrioid endometrial carcinomas remain a clinical dilemma, with some tumors behaving as the low-grade counterparts and others presenting a more aggressive behavior.
OBJECTIVES
To determine the association between POLE mutational status and the overall-survival (OS) and progression-free-survival (PFS) of patients with G3 endometrioid endometrial cancer (EC). We also aimed to determine the prevalence of POLE mutations in G3 endometrioid EC.
METHODS
We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO No: CRD4202340008). We searched the following electronic databases: PubMed/Medline, EMBASE, Cochrane Library, Scopus, and Web of Science. For time-to-event data, the effect of POLE mutation in G3 EC was described using hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Individual patient data for each study was investigated if available from the study authors. If individual patient data were not available, information regarding time-to-event outcomes was extracted using an appropriate methodology. OS and PFS were analyzed using both one-stage and two-stage approaches, the Kaplan-Meier method, and Cox-proportional hazards models.
RESULTS
This systematic review and meta-analysis included 19 studies with 3092 patients who had high-grade endometrioid EC. Patients with POLE mutations had lower risks of death (HR = 0.36, 95% CI 0.26 to 0.50, I = 0%, 10 trials) and disease progression (HR = 0.31, 95% CI 0.17 to 0.57, I = 33%, 10 trials). The pooled prevalence of POLE mutation was 11% (95% CI 9 to 13, I = 68%, 18 studies).
CONCLUSION
POLE mutations in high-grade endometrioid EC are associated with a more favorable prognosis with increased OS and PFS.
Topics: Female; Humans; Neoplasm Grading; Poly-ADP-Ribose Binding Proteins; Carcinoma, Endometrioid; Prognosis; Mutation; Endometrial Neoplasms
PubMed: 38262245
DOI: 10.1016/j.ygyno.2024.01.018 -
BioMed Research International 2022Globally, colorectal carcinoma (CRC) is the third most common cancer and the third major cause of cancer-related death in both sexes. KRAS and BRAF mutations are almost... (Meta-Analysis)
Meta-Analysis
Globally, colorectal carcinoma (CRC) is the third most common cancer and the third major cause of cancer-related death in both sexes. KRAS and BRAF mutations are almost mutually exclusively involved in the pathogenesis of CRC. Both are major culprits in treatment failure and poor prognosis for CRC. . A systematic review and meta-analysis of various research was done following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. This trial is registered with PROSPERO CRD42021256452. The initial search included 646 articles; after the removal of noneligible studies, a total of 88 studies was finally selected. Data analysis was carried out using OpenMeta Analyst and Comprehensive Meta-Analysis 3.0 (CMA 3.0) software to investigate the prevalence of KRAS and BRAF mutations among patients with CRC in Asia. . The meta-analysis comprises of 25,525 sample sizes from Asia with most being male 15,743/25525 (61.7%). Overall prevalence of KRAS mutations was (59/88) 36.3% (95% CI: 34.5-38.2) with = 85.54% ( value < 0.001). In 43/59 studies, frequency of KRAS mutations was majorly in codon 12 (76.6% (95% CI: 74.2-78.0)) and less in codon 13 (21.0% (95% CI: 19.1-23.0)). Overall prevalence of BRAF mutations was 5.6% (95% CI: 3.9-8.0) with = 94.00% ( value < 0.001). When stratified according to location, a higher prevalence was observed in Indonesia (71.8%) while Pakistan has the lowest (13.5%). . Total prevalence of KRAS and BRAF mutations in CRC was 36.6% and 5.6%, respectively, and the results conformed with several published studies on KRAS and BRAF mutations.
Topics: Biomarkers; Codon; Colorectal Neoplasms; Female; Humans; Male; Mutation; Pakistan; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras)
PubMed: 35782059
DOI: 10.1155/2022/5824183