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Cancers Dec 2022Single-nucleotide polymorphisms (SNPs) play an essential role in various malignancies, but their role in cholangiocarcinoma (CCA) remains to be elucidated. Therefore,... (Review)
Review
Single-nucleotide polymorphisms (SNPs) play an essential role in various malignancies, but their role in cholangiocarcinoma (CCA) remains to be elucidated. Therefore, the purpose of this systematic review was to evaluate the association between SNPs and CCA, focusing on tumorigenesis and prognosis. A systematic literature search was carried out using PubMed, Embase, Web of Science and the Cochrane database for the association between SNPs and CCA, including literature published between January 2000 and April 2022. This systematic review compiles 43 SNPs in 32 genes associated with CCA risk, metastatic progression and overall prognosis based on 34 studies. Susceptibility to CCA was associated with SNPs in genes related to inflammation (PTGS2/COX2, IL6, IFNG/IFN-γ, TNF/TNF-α), DNA repair (ERCC1, MTHFR, MUTYH, XRCC1, OGG1), detoxification (NAT1, NAT2 and ABCC2), enzymes (SERPINA1, GSTO1, APOBEC3A, APOBEC3B), RNA (HOTAIR) and membrane-based proteins (EGFR, GAB1, KLRK1/NKG2D). Overall oncological prognosis was also related to SNPs in eight genes (GNB3, NFE2L2/NRF2, GALNT14, EGFR, XRCC1, EZH2, GNAS, CXCR1). Our findings indicate that multiple SNPs play different roles at various stages of CCA and might serve as biomarkers guiding treatment and allowing oncological risk assessment. Considering the differences in SNP detection methods, patient ethnicity and corresponding environmental factors, more large-scale multicentric investigations are needed to fully determine the potential of SNP analysis for CCA susceptibility prediction and prognostication.
PubMed: 36497451
DOI: 10.3390/cancers14235969 -
La Clinica Terapeutica 2023Cancer, a potentially fatal condition, is one of the leading causes of death worldwide. Among males aged 20 to 35, the most common cancer in healthy individuals is... (Review)
Review
BACKGROUND
Cancer, a potentially fatal condition, is one of the leading causes of death worldwide. Among males aged 20 to 35, the most common cancer in healthy individuals is testicular cancer, accounting for 1% to 2% of all cancers in men.
METHODS
Throughout this review, we have employed a targeted research approach, carefully handpicking the most representative and relevant articles on the subject. Our methodology involved a systematic review of the scientific literature to ensure a comprehensive and accurate overview of the available sources.
RESULTS
The onset and spread of testicular cancer are significantly influenced by genetic changes, including mutations in oncogenes, tu-mor suppressor genes, and DNA repair genes. As a result of identifying these specific genetic mutations in cancers, targeted medications have been developed to disrupt the signaling pathways affected by these genetic changes. To improve the diagnosis and treatment of this disease, it is crucial to understand its natural and clinical histories.
CONCLUSIONS
In order to comprehend cancer better and to discover new biomarkers and therapeutic targets, oncologists are increasingly employing omics methods, such as genomics, transcriptomics, proteomics, and metabolomics. Targeted medications that focus on specific genetic pathways and mutations hold promise for advancing the diagnosis and management of this disease.
Topics: Humans; Male; Testicular Neoplasms; Precision Medicine; Genomics; Proteomics
PubMed: 37994745
DOI: 10.7417/CT.2023.2468 -
The World Journal of Men's Health Apr 2024Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). However, it remains unclear whether varicocele repair (VR) could...
Effects of Varicocele Repair on Sperm DNA Fragmentation and Seminal Malondialdehyde Levels in Infertile Men with Clinical Varicocele: A Systematic Review and Meta-Analysis.
PURPOSE
Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). However, it remains unclear whether varicocele repair (VR) could reduce these parameters. This systematic review and meta-analysis (SRMA) aims to investigate the impact of VR on SDF and seminal malondialdehyde (MDA).
MATERIALS AND METHODS
A literature search was performed in Scopus, PubMed, Ovid, Embase, and Cochrane databases. This SRMA included randomized controlled trials and observational studies reporting the pre- and postoperative levels of SDF and seminal OS in infertile men with clinical varicocele that underwent VR. Subgroup analyses included techniques of VR and SDF testing. The effect size was expressed as standardized mean difference (SMD).
RESULTS
Out of 1,632 abstracts assessed for eligibility, 29 studies with 1,491 infertile men were included. The analysis showed a significant reduction in SDF after VR, compared to preoperative values (SMD -1.125, 95% confidence interval [CI] -1.410, -0.840; p<0.0001) with high inter-study heterogeneity (I²=90.965%). Reduction in SDF was evident with microsurgical technique and non-microsurgical inguinal approaches (SMD -1.014, 95% CI -1.263, -0.765; p<0.0001, and SMD -1.495, 95% CI -2.116, -0.873; p<0.0001), respectively. Reduction in SDF was significant irrespective of testing was done by sperm chromatin dispersion (SMD -2.197, 95% CI -3.187, -1.207; p<0.0001), sperm chromatin structure assay (SMD -0.857, 95% CI -1.156, -0.559; p<0.0001) or TUNEL (SMD -1.599, 95% CI -2.478, -0.719; p<0.0001). A significant decrease in seminal MDA levels was observed following VR (SMD -2.450, 95% CI -3.903 to -0.997, p=0.001) with high inter-study heterogeneity (I²=93.7%).
CONCLUSIONS
Using pre- and post-intervention data, this SRMA indicates a significant reduction in SDF and seminal MDA levels in infertile men with clinical varicocele treated with VR. These findings may have important implications for the future management of this selected group of infertile patients.
PubMed: 38164034
DOI: 10.5534/wjmh.230235 -
Life (Basel, Switzerland) Dec 2022The aim of the present review was to assess the impact of DNA damage repair (DDR) mutations on response and outcome of patients (pts) affected by advanced prostate... (Review)
Review
The aim of the present review was to assess the impact of DNA damage repair (DDR) mutations on response and outcome of patients (pts) affected by advanced prostate cancer (PCa) submitted to radionuclide therapies with [223Ra]RaCl2 (223Ra-therapy) or prostate specific membrane antigen (PSMA) ligands. A systematic literature search according to PRISMA criteria was made by using two main databases. Only studies published up until to October 2022 in the English language with ≥10 enrolled patients were selected. Seven studies including 326 pts, of whom 201 (61.6%) harboring DDR defects, were selected. The majority of selected papers were retrospective and four out of seven (57.1%) had small sample size (<50 pts). Three out of seven (42.8%) studies reported a more favorable outcome (overall or progression free survival) after therapy with alpha emitters (223Ra-therapy or [225Ac]Ac-PSMA-617) in subjects with DDR defects with respect to those without mutations. In two studies employing alpha or beta emitters ([177Lu]/[225Ac]-PMSA), no significant benefit was registered in pts harboring DDR defects. In all but one paper, no significant difference in response rate was reported among pts with or without DDR mutations. Although preliminary and biased by the retrospective design, preliminary data suggest a trend towards a longer survival in PCa pts harboring DDR defects submitted to radionuclide targeted therapy with alpha emitters.
PubMed: 36676004
DOI: 10.3390/life13010055 -
Antioxidants & Redox Signaling Apr 20168-Hydroxy-2-deoxyguanosine (8-OHdG) is generated after the repair of ROS-mediated DNA damages and, thus, is one of the most widely recognized biomarkers of oxidative... (Meta-Analysis)
Meta-Analysis Review
SIGNIFICANCE
8-Hydroxy-2-deoxyguanosine (8-OHdG) is generated after the repair of ROS-mediated DNA damages and, thus, is one of the most widely recognized biomarkers of oxidative damage of DNA because guanosine is the most oxidized among the DNA nucleobases. In several pathological conditions, high urinary levels of oxidized DNA-derived metabolites have been reported (e.g., cancer, atherosclerosis, hypertension, and diabetes).
RECENT ADVANCES
Even if published studies have shown that DNA damage is significantly associated with the development of atherosclerosis, the exact role of this damage in the onset and progression of this pathology is not fully understood, and the association of oxidative damage to DNA with cardiovascular disease (CVD) still needs to be more extensively investigated. We performed a meta-analysis of the literature to investigate the association among 8-OHdG levels and CVD.
CRITICAL ISSUES
Fourteen studies (810 CVD patients and 1106 controls) were included in the analysis. We found that CVD patients showed higher 8-OHdG levels than controls (SMD: 1.04, 95%CI: 0.61, 1.47, p < 0.001, I(2) = 94%, p < 0.001). The difference was confirmed both in studies in which 8-OHdG levels were assessed in urine (MD: 4.43, 95%CI: 1.71, 7.15, p = 0.001) and in blood samples (MD: 1.42, 95%CI: 0.64, 2.21, p = 0.0004). Meta-regression models showed that age, hypertension, and male gender significantly impacted on the difference in 8-OHdG levels among CVD patients and controls.
FUTURE DIRECTIONS
8-OHdG levels are higher in patients with CVD than in controls. However, larger prospective studies are needed to test 8-OHdG as a predictor of CVD.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Deoxyguanosine; Humans; Oxidation-Reduction; Oxidative Stress; Prognosis; Publication Bias; Regression Analysis
PubMed: 26650622
DOI: 10.1089/ars.2015.6508 -
Frontiers in Oncology 2022The variants of DNA repair genes have been widely reported to be associated with cancer risk in the past decades. As were two crucial members of nucleotide excision...
The variants of DNA repair genes have been widely reported to be associated with cancer risk in the past decades. As were two crucial members of nucleotide excision repair pathway, and polymorphisms are linked with susceptibility to multiple cancers, but the conclusions were controversial. In this updated meta-analysis concerned with and single-nucleotide polymorphisms (SNPs), 160 eligible publications were identified, and we exerted the meta-analysis of correlations between 24 variants and 19 types of cancer. Venice criteria and the false-positive report probability were used to evaluate a cumulative evidence of significant associations. We conducted functional annotations for those strong associations using data from the Encyclopedia of DNA Elements (ENCODE) Project. We obtained 11 polymorphisms significantly related to changed susceptibility to 11 cancers ( < 0.05). Strong evidence was assigned to four variant-related cancer risks in Asians ( rs744154 with bladder cancer, rs2296147 with esophageal cancer, rs17655 with laryngeal cancer and uterine cancer, and rs751402 with gastric cancer), moderate to six SNPs with a risk of eight cancers, and weak to nine SNPs with nine cancers. Data from ENCODE and other public databases showed that the loci of these SNPs with strong evidence might fall in putative functional regions. In conclusion, this paper summarizes comprehensive evidence that common variants of and genes are strongly associated with the risk of bladder cancer, esophageal cancer, laryngeal cancer, uterine cancer, and gastric cancer and elucidates the crucial role of the DNA repair genes in the genetic predisposition to human cancers.
PubMed: 36033436
DOI: 10.3389/fonc.2022.951193 -
Frontiers in Oncology 2023Numerous reviews of the epidemiology and risk factors for breast cancer have been published previously which heighted different directions of breast cancer.
BACKGROUND
Numerous reviews of the epidemiology and risk factors for breast cancer have been published previously which heighted different directions of breast cancer.
AIM
The present review examined the likelihood that incidence, prevalence, and particular risk factors might vary by geographic region and possibly by food and cultural practices as well.
METHODS
A systematic review (2017-2022) was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, reporting on epidemiological and risk factor reports from different world regions. Medical Subject Heading (MeSH) terms: "Breast neoplasm" "AND" country terms such as "Pakistan/epidemiology", "India/epidemiology", "North America/epidemiology", "South Africa/epidemiology" were used to retrieve 2068 articles from PubMed. After applying inclusion and exclusion terms, 49 papers were selected for systematic review.
RESULTS
Results of selected articles were summarized based on risk factors, world regions and study type. Risk factors were classified into five categories: demographic, genetic and lifestyle risk factors varied among countries. This review article covers a variety of topics, including regions, main findings, and associated risk factors such as genetic factors, and lifestyle. Several studies revealed that lifestyle choices including diet and exercise could affect a person's chance of developing breast cancer. Breast cancer risk has also been linked to genetic variables, including DNA repair gene polymorphisms and mutations in the breast cancer gene (BRCA). It has been found that most of the genetic variability links to the population of Asia while the cause of breast cancer due to lifestyle modifications has been found in American and British people, indicating that demographic, genetic, and, lifestyle risk factors varied among countries.
CONCLUSION
There are many risk factors for breast cancer, which vary in their importance depending on the world region. However, further investigation is required to better comprehend the particular causes of breast cancer in these areas as well as to create efficient prevention and treatment plans that cater to the local population.
PubMed: 37886170
DOI: 10.3389/fonc.2023.1240098 -
Medical Oncology (Northwood, London,... Feb 2015The oxyguanine glycosylase 1 (OGG1) gene has an important role in DNA repair, and the polymorphism of the gene may alter cancer susceptibility. This study aims to... (Meta-Analysis)
Meta-Analysis Review
The oxyguanine glycosylase 1 (OGG1) gene has an important role in DNA repair, and the polymorphism of the gene may alter cancer susceptibility. This study aims to examine the association between the OGG1 Ser326Cys polymorphism and cancer risk based on meta-analysis. Relevant studies were identified through a search of PubMed and Weipu databases, and a total of 109 studies including 111 comparisons containing 34,041 cases and 42,730 controls were enrolled. Overall, significant association was observed between OGG1 Ser326Cys polymorphism and cancer risk in all genetic models except for heterozygote model (Cys/Cys + Cys/Ser vs Ser/Ser: OR 1.071, 95 % CI 1.019-1.125; Cys/Cys vs Cys/Ser + Ser/Ser: OR 1.159, 95 % CI 1.076-1.248; Cys/Cys vs Ser/Ser: OR 1.202, 95 % CI 1.105-1.308). In stratified analysis by cancer type, significantly increased cancer risk was observed in digestive system cancer, head and neck cancer and lung cancer. For gynecologic cancer, significantly increased cancer risk was also observed in homozygote model (OR 1.974, 95 % CI 1.254-3.107). In addition, in stratified analysis by ethnicities, increased cancer risk was found in Asians (Cys/Cys vs Cys/Ser + Ser/Ser: OR 1.195, 95 % CI 1.088-1.313; Cys/Cys + Cys/Ser vs Ser/Ser: OR 1.115, 95 % CI 1.045-1.190; Cys/Cys vs Ser/Ser: OR 1.273, 95 % CI 1.149-1.410). The OGG1 Ser326Cys polymorphism may be a risk factor for cancers of lung, digestive system and head and neck.
Topics: DNA Glycosylases; Genetic Predisposition to Disease; Genotype; Humans; Neoplasms; Polymorphism, Single Nucleotide
PubMed: 25588927
DOI: 10.1007/s12032-014-0472-z -
European Journal of Medical Genetics Feb 2016A DNA repair protein, X-ray repair cross-complementing group 1 (XRCC1), has been implicated in the development of multiple cancers, including non-Hodgkin lymphoma (NHL).... (Meta-Analysis)
Meta-Analysis Review
A DNA repair protein, X-ray repair cross-complementing group 1 (XRCC1), has been implicated in the development of multiple cancers, including non-Hodgkin lymphoma (NHL). Recent studies evaluating the association between XRCC1 polymorphisms and NHL risk have been published. However, the published studies are controversial. This systematic review and meta-analysis of case-control studies aimed to evaluate the association between three single nucleotide polymorphisms (SNPs) of XRCC1, Arg194Trp, Arg280His and Arg399Gln, with risk for developing NHL. We conducted a comprehensive literature search using PubMed, Embase, and the Cochrane Library databases for relevant studies regarding the association between XRCC1 SNPs and NHL risk. Thirteen published case-control studies involving the Arg194Trp (3897 cases and 5371 controls), Arg280His (2140 cases and 3158 controls) and Arg399Gln (2722 cases and 4856 controls) SNPs were selected for meta-analysis. The Arg194Trp SNP was associated with increased NHL risk within the Asian population, and increased diffuse large B cell lymphoma (DLBCL) risk within the overall population under dominant model. The Arg399Gln SNP was associated with decreased risk for NHL and DLBCL under heterozygous and dominant models of inheritance. The Arg280His SNP was not associated with NHL risk by overall or subgroup analyses.
Topics: DNA-Binding Proteins; Genetic Predisposition to Disease; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Polymorphism, Single Nucleotide; X-ray Repair Cross Complementing Protein 1
PubMed: 26723520
DOI: 10.1016/j.ejmg.2015.12.011 -
Journal of Affective Disorders Jun 2022In vivo and in vitro studies suggest that inflammation and oxidative damage may contribute to the pathogenesis of major depressive disorder (MDD) and bipolar disorder... (Review)
Review
BACKGROUND
In vivo and in vitro studies suggest that inflammation and oxidative damage may contribute to the pathogenesis of major depressive disorder (MDD) and bipolar disorder (BD). Imbalance between DNA damage and repair is an emerging research area examining pathophysiological mechanisms of these major mood disorders. This systematic review sought to review DNA repair enzymes, with emphasis on the base excision repair (BER), in mood disorders.
METHODS
We conducted a comprehensive literature search of Ovid MEDLINE® Epub Ahead of Print, Ovid MEDLINE® In-Process & Other Non-Indexed Citations, Ovid MEDLINE® Daily, EMBASE (1947), and PsycINFO for studies investigating the alterations in base excision repair in patients with MDD or BD.
RESULTS
A total of 1364 records were identified. 1352 records remained after duplicates were removed. 24 records were selected for full-text screening and a remaining 12 articles were included in the qualitative synthesis. SNPs (single nucleotide polymorphisms) of several BER genes have been shown to be associated with MDD and BD. However, it was difficult to draw conclusions from BER gene expression studies due to conflicting findings and the small number of studies.
LIMITATIONS
All studies were correlational so it was not possible to draw conclusions regarding causality.
CONCLUSION
Future studies comparing DNA repair during the manic or depressive episode to remission will give us a better insight regarding the role of DNA repair in mood disorders. These alterations might be utilized as diagnostic and prognostic biomarkers as well as measuring treatment response.
Topics: Bipolar Disorder; DNA Repair; Depressive Disorder, Major; Humans; Mood Disorders; Polymorphism, Single Nucleotide
PubMed: 35306122
DOI: 10.1016/j.jad.2022.03.033