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Gynecologic and Obstetric Investigation Apr 2024DNA methylation plays an important role in the carcinogenesis, progression, and prognosis of various human cancers. RASSF1A, BRCA1, APC, and p16 are the frequently...
INTRODUCTION
DNA methylation plays an important role in the carcinogenesis, progression, and prognosis of various human cancers. RASSF1A, BRCA1, APC, and p16 are the frequently methylated genes among patients with ovarian cancer. Therefore, our study aimed to better determine the prognostic and cancer characteristics effects of RASSF1A, BRCA1, APC, and p16 promoter methylation in ovarian cancer patients.
METHODS
Databases such as PubMed, Web of Science, EMBASE, CNKI, and WanFang were searched for published studies up to March 4, 2024. The outcomes are shown as OR and HR with their 95% CIs. Then, the random or fixed-effect model was performed to evaluate the effect sizes.
RESULTS
Finally, 27 articles were included in this meta-analysis. No significant relationships were observed between RASSF1A, BRCA1, and APC promoter methylation and the clinical prognostic (including overall survival and progression-free survival) and cancer characteristics (including ascites, lymph node metastasis, and pelvic peritoneal metastasis) in ovarian cancer. p16 promoter methylation was significantly related to poor progression-free survival (PFS) (HR = 1.52, 95% CI = 1.14-2.04) and overall survival (OS) (HR = 1.39, 95% CI = 1.06, to 1.83) in univariate and poor PFS in multivariate Cox regression models (HR = 1.42, 95% CI = 1.05-1.92). Besides, our results indicated that the clinical stage was associated with inferior OS while there was no significant association between tumor grade and OS.
CONCLUSION
RASSF1A, BRCA1, and APC promoter methylation were not significantly associated with clinical prognostic and cancer characteristics. p16 may be a useful biomarker for predicting PFS in ovarian cancer. Furthermore, the clinical stage was significantly associated with OS. In further research, more prospective and multicenter validation studies remain needed.
PubMed: 38615670
DOI: 10.1159/000538673 -
Pancreas Sep 2018Pancreatic cancer requires many genetic mutations. Combinations of underlying germline variants and environmental factors may increase the risk of cancer and accelerate...
Pancreatic cancer requires many genetic mutations. Combinations of underlying germline variants and environmental factors may increase the risk of cancer and accelerate the oncogenic process. We systematically reviewed, annotated, and classified previously reported pancreatic cancer-associated germline variants in established risk genes. Variants were scored using multiple criteria and binned by evidence for pathogenicity, then annotated with published functional studies and associated biological systems/pathways. Twenty-two previously identified pancreatic cancer risk genes and 337 germline variants were identified from 97 informative studies that met our inclusion criteria. Fifteen of these genes contained 66 variants predicted to be pathogenic (APC, ATM, BRCA1, BRCA2, CDKN2A, CFTR, CHEK2, MLH1, MSH2, NBN, PALB2, PALLD, PRSS1, SPINK1, TP53). Pancreatic cancer risk genes were organized into key biological mechanisms that promote pancreatic oncogenesis within an oncogenic model. Development of precision medicine approaches requires updated variant information within the framework of an oncogenic progression model. Complex risk modeling may improve interpretation of early biomarkers and guide pathway-specific treatment for pancreatic cancer in the future. Precision medicine is within reach.
Topics: Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Pancreatic Neoplasms; Proto-Oncogene Proteins; Risk Assessment; Risk Factors
PubMed: 30113427
DOI: 10.1097/MPA.0000000000001136 -
Familial Cancer Jan 2019Thyroid cancer (TC) is a known extra-intestinal manifestation and contributes to the mortality and morbidity in patients with familial adenomatous polyposis (FAP). Its... (Meta-Analysis)
Meta-Analysis
Thyroid cancer (TC) is a known extra-intestinal manifestation and contributes to the mortality and morbidity in patients with familial adenomatous polyposis (FAP). Its exact prevalence is not well established and recent studies have shown an increasing number of TC in this patient population. The prevalence of benign thyroid masses and endocrinologic thyroid disorders are also poorly described. We conducted a systematic review and meta-analysis by using a random-effects model to characterize TC and estimated the prevalence of thyroid diseases in FAP patients. Twelve studies (n = 9821) were included. Pooled prevalence of TC, benign thyroid masses, and endocrinologic thyroid disorders in FAP were 2.6% [95% confidence interval (CI) 1.3-4.8], 48.8% [95% CI 33.8-64.0], and 6.9% [95% CI 4.5-10.3] respectively. Subgroup analyses revealed higher prevalence of TC in studies with fewer participants, studies that used screening ultrasound to diagnose TC, and studies that were published after 2002. TC diagnosis preceded the diagnosis of FAP in 34% of the patients. The means age at diagnosis of FAP and TC were 29 and 31 years, respectively. 95% of the patients were female and the most common pathology was of papillary subtype (83.3%). Most mutations (79.2%) were located at the 5' end of APC gene. In summary, benign thyroid disorders are common in FAP, yet, TC is an uncommon phenomenon. Certain patient subset, such as young female with APC mutation at the 5' end, might benefit from routine surveillance ultrasound.
Topics: Adenomatous Polyposis Coli; Adenomatous Polyposis Coli Protein; Adult; Age Factors; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Mutation; Prevalence; Sex Factors; Thyroid Neoplasms
PubMed: 29663106
DOI: 10.1007/s10689-018-0085-3 -
Critical Reviews in Oncology/hematology Aug 2021Despite conventional measures of future polyp risk (histology, dysplasia, size, number), surveillance places a burden on patients and colonoscopy services. We aimed to... (Review)
Review
INTRODUCTION
Despite conventional measures of future polyp risk (histology, dysplasia, size, number), surveillance places a burden on patients and colonoscopy services. We aimed to review novel risk stratification techniques.
METHODS
A systematic literature review was performed for studies using genomics, transcriptomics, IHC or microbiome as markers of metachronous polyp risk.
RESULTS
4165 papers underwent title, 303 abstract and 215 full paper review. 25 papers were included. 49 mutations/ SNPs/ haplotypes in 23 genes/ chromosomal regions (KRAS, APC, EGFR, COX1/2, IL23R, DRD2, CYP2C9/24A1/7A1, UGT1A6, ODC, ALOX12/15, PGDH, SRC, IGSF5, KCNS3, EPHB1/ KY, FAM188b, 3p24.1, 9q33.2, 13q33.2) correlated with metachronous adenoma / advanced adenoma risk. Expression levels of 6 proteins correlated with metachronous adenoma (p53, β-catenin, COX2, Adnab-9, ALDH1A1) or sessile serrated polyp (ANXA10) risk.
CONCLUSION
Although genomic and IHC markers correlated with metachronous polyp risk, it seems likely that a panel of novel markers will be required to refine this risk.
Topics: Adenoma; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Humans; Hyperplasia
PubMed: 34246774
DOI: 10.1016/j.critrevonc.2021.103421 -
Scientific Reports Oct 2020The present study was conducted to evaluate the prevalence of the signaling pathways mutation rate in the Gastrointestinal (GI) tract cancers in a systematic review and... (Meta-Analysis)
Meta-Analysis
The present study was conducted to evaluate the prevalence of the signaling pathways mutation rate in the Gastrointestinal (GI) tract cancers in a systematic review and meta-analysis study. The study was performed based on the PRISMA criteria. Random models by confidence interval (CI: 95%) were used to calculate the pooled estimate of prevalence via Metaprop command. The pooled prevalence indices of signal transduction pathway mutations in gastric cancer, liver cancer, colorectal cancer, and pancreatic cancer were 5% (95% CI: 3-8%), 12% (95% CI: 8-18%), 17% (95% CI: 14-20%), and 20% (95% CI: 5-41%), respectively. Also, the mutation rates for Wnt pathway and MAPK pathway were calculated to be 23% (95% CI, 14-33%) and 20% (95% CI, 17-24%), respectively. Moreover, the most popular genes were APC (in Wnt pathway), KRAS (in MAPK pathway) and PIK3CA (in PI3K pathway) in the colorectal cancer, pancreatic cancer, and gastric cancer while they were beta-catenin and CTNNB1 in liver cancer. The most altered pathway was Wnt pathway followed by the MAPK pathway. In addition, pancreatic cancer was found to be higher under the pressure of mutation compared with others based on pooled prevalence analysis. Finally, APC mutations in colorectal cancer, KRAS in gastric cancer, and pancreatic cancer were mostly associated gene alterations.
Topics: Adenomatous Polyposis Coli Protein; Class I Phosphatidylinositol 3-Kinases; DNA Mutational Analysis; Gastrointestinal Neoplasms; Humans; MAP Kinase Signaling System; Mutation; Prevalence; Proto-Oncogene Proteins p21(ras); Signal Transduction; Wnt Signaling Pathway
PubMed: 33127962
DOI: 10.1038/s41598-020-73770-1 -
Cancer Genetics Apr 2024Early detection of breast cancer would help alleviate the burden of treatment for early-stage breast cancer and help patient prognosis. There is currently no established...
BACKGROUND
Early detection of breast cancer would help alleviate the burden of treatment for early-stage breast cancer and help patient prognosis. There is currently no established gene panel that utilizes the potential of DNA methylation as a molecular signature for the early detection of breast cancer. This systematic review aims to identify the optimal methylation biomarkers for a non-invasive liquid biopsy assay and the gaps in knowledge regarding biomarkers for early detection of breast cancer.
METHODS
Following the PRISMA-ScR method, Pubmed and Google Scholar was searched for publications related to methylation biomarkers in breast cancer over a five-year period. Eligible publications were mined for key data fields such as study aims, cohort demographics, types of breast cancer studied, technologies used, and outcomes. Data was analyzed to address the objectives of the review.
RESULTS
Literature search identified 112 studies of which based on eligibility criteria, 13 studies were included. 28 potential methylation gene targets were identified, of which 23 were methylated at the promoter region, 1 was methylated in the body of the gene and 4 were methylated at yet to be identified locations.
CONCLUSIONS
Our evaluation shows that at minimum APC, RASSFI, and FOXA1 genes would be a promising set of genes to start with for the early detection of breast cancer, based on the sensitivity and specificity outlined in the studies. Prospective studies are needed to optimize biomarkers for broader impact in early detection of breast cancer.
Topics: Female; Humans; Biomarkers, Tumor; Breast Neoplasms; DNA Methylation; Early Detection of Cancer; Prognosis; Sensitivity and Specificity
PubMed: 38134587
DOI: 10.1016/j.cancergen.2023.12.003 -
The British Journal of Nutrition Mar 2020During pregnancy, changes occur to influence the maternal gut microbiome, and potentially the fetal microbiome. Diet has been shown to impact the gut microbiome. Little...
During pregnancy, changes occur to influence the maternal gut microbiome, and potentially the fetal microbiome. Diet has been shown to impact the gut microbiome. Little research has been conducted examining diet during pregnancy with respect to the gut microbiome. To meet inclusion criteria, dietary analyses must have been conducted as part of the primary aim. The primary outcome was the composition of the gut microbiome (infant or maternal), as assessed using culture-independent sequencing techniques. This review identified seven studies for inclusion, five examining the maternal gut microbiome and two examining the fetal gut microbiome. Microbial data were attained through analysis of stool samples by 16S rRNA gene-based microbiota assessment. Studies found an association between the maternal diet and gut microbiome. High-fat diets (% fat of total energy), fat-soluble vitamins (mg/day) and fibre (g/day) were the most significant nutrients associated with the gut microbiota composition of both neonates and mothers. High-fat diets were significantly associated with a reduction in microbial diversity. High-fat diets may reduce microbial diversity, while fibre intake may be positively associated with microbial diversity. The results of this review must be interpreted with caution. The number of studies was low, and the risk of observational bias and heterogeneity across the studies must be considered. However, these results show promise for dietary intervention and microbial manipulation in order to favour an increase of health-associated taxa in the gut of the mother and her offspring.
PubMed: 32129734
DOI: 10.1017/S0007114520000847 -
The British Journal of Surgery May 2024Hereditary adenomatous polyposis syndromes, including familial adenomatous polyposis and other rare adenomatous polyposis syndromes, increase the lifetime risk of...
Updated European guidelines for clinical management of familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), gastric adenocarcinoma, proximal polyposis of the stomach (GAPPS) and other rare adenomatous polyposis syndromes: a joint EHTG-ESCP revision.
BACKGROUND
Hereditary adenomatous polyposis syndromes, including familial adenomatous polyposis and other rare adenomatous polyposis syndromes, increase the lifetime risk of colorectal and other cancers.
METHODS
A team of 38 experts convened to update the 2008 European recommendations for the clinical management of patients with adenomatous polyposis syndromes. Additionally, other rare monogenic adenomatous polyposis syndromes were reviewed and added. Eighty-nine clinically relevant questions were answered after a systematic review of the existing literature with grading of the evidence according to Grading of Recommendations, Assessment, Development, and Evaluation methodology. Two levels of consensus were identified: consensus threshold (≥67% of voting guideline committee members voting either 'Strongly agree' or 'Agree' during the Delphi rounds) and high threshold (consensus ≥ 80%).
RESULTS
One hundred and forty statements reached a high level of consensus concerning the management of hereditary adenomatous polyposis syndromes.
CONCLUSION
These updated guidelines provide current, comprehensive, and evidence-based practical recommendations for the management of surveillance and treatment of familial adenomatous polyposis patients, encompassing additionally MUTYH-associated polyposis, gastric adenocarcinoma and proximal polyposis of the stomach and other recently identified polyposis syndromes based on pathogenic variants in other genes than APC or MUTYH. Due to the rarity of these diseases, patients should be managed at specialized centres.
Topics: Humans; Adenomatous Polyposis Coli; Stomach Neoplasms; Adenocarcinoma; DNA Glycosylases; Neoplastic Syndromes, Hereditary; Europe; Adenomatous Polyps; Polyps
PubMed: 38722804
DOI: 10.1093/bjs/znae070 -
Clinical and Experimental Medicine Feb 2020Several meta-analyses have evaluated the value of biomarkers in diagnosing breast cancer, but which biomarker has the optimal diagnostic value remains unclear. This... (Comparative Study)
Comparative Study
Several meta-analyses have evaluated the value of biomarkers in diagnosing breast cancer, but which biomarker has the optimal diagnostic value remains unclear. This overview aimed to compare the accuracy of different biomarkers in diagnosing breast cancer. PubMed, Embase.com, the Cochrane Library of Systematic Reviews, and Web of Science were searched. The assessment of multiple systematic reviews-2 (AMSTAR-2) was used to assess the methodological quality and preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy (PRISMA-DTA) for reporting quality. Pairwise meta-analyses were performed to estimate the pooled results for each biomarker, and indirect comparisons were conducted to compare diagnostic accuracy between biomarkers. Eleven systematic reviews (SRs) involving 218 original studies were included. All SRs were of critically low methodological quality, 3 SRs had minimal reporting flaws and 8 SRs had minor flaws. The pooled sensitivity and specificity were 0.77 and 0.87 for miRNA, 0.70 and 0.87 for circulating cell-free DNA, 0.29 and 0.96 for APC gene promoter methylation, 0.69 and 0.99 for 14-3-3σ promoter methylation, 0.63 and 0.82 for CA153, 0.58 and 0.87 for CEA, and 0.73 and 0.56 for PSA. Compared with CA153 and PSA, miRNA had a higher sensitivity and specificity. The sensitivity of miRNA was higher than circulating cell-free DNA and CEA, although they had the same specificities. APC gene promoter methylation and 14-3-3σ promoter methylation were more specific than miRNA, but they had unacceptably low sensitivity. In conclusion, miRNA had better diagnostic accuracy than the other six biomarkers. But due to the low quality of included SRs, the results need to be interpreted with caution. Further study should investigate the diagnostic accuracy of different biomarkers in direct comparisons and focus on the value of combined biomarkers.
Topics: 14-3-3 Proteins; Adenomatous Polyposis Coli Protein; Antigens, Neoplasm; Biomarkers, Tumor; Breast Neoplasms; Carcinoembryonic Antigen; Cell-Free Nucleic Acids; DNA Methylation; Exoribonucleases; Female; Humans; MicroRNAs; Promoter Regions, Genetic; Sensitivity and Specificity
PubMed: 31894424
DOI: 10.1007/s10238-019-00598-z -
Biology of Sport Oct 2021Each athlete's innate talent is widely recognized as one of the important contributors to achievement in athletic performance, and genetic factors determine a...
Each athlete's innate talent is widely recognized as one of the important contributors to achievement in athletic performance, and genetic factors determine a significant portion of talent or traits. Advances in DNA sequencing technology allow us to discover specific genetic variants contributing to these traits in sports performance. The objective of this systematic review is to identify genes that may play a significant role in the performance of elite-level combat sports athletes. Through the review of 18 full-text articles, a total of 109 different polymorphisms were investigated in 14,313 participants (2,786 combat sports athletes, 8,969 non-athlete controls, 2,558 other sports athletes). Thirteen polymorphisms showed a significant difference between elite combat athletes and the control group, and consist of 8 (PPARA rs4253778, ACTN3 rs1815739, ACE rs4646994, CKM rs8111989, MCT1 rs1049434, FTO rs9939609, GABP1 rs7181866 and rs8031031) oriented to athletic performance and 5 (COMT rs4680, FEV rs860573, SLC6A2 rs2242446, HTR1B rs11568817, ADRA2A rs521674) focused on psychological traits including emotional and mental traits in combat sports athletes. In addition, a recent whole genome sequencing study identified 4 polymorphisms (KIF27 rs10125715, APC rs518013, TMEM229A rs7783359, LRRN3 rs80054135) associated with reaction time in wrestlers. However, it is not clearly identified which genes are linked explicitly with elite combat sports athletes and how they affect the elite athlete's status or performance in combat sports. Hence, a greater number of candidate genes should be included in future studies to practically utilize the genetic information.
PubMed: 34937977
DOI: 10.5114/biolsport.2022.102864