-
International Journal of Biometeorology Nov 2022Thermal stress has a direct effect on various types of DNA damage, which depends on the stage of the cell cycle when the cell is exposed to different climate conditions.... (Review)
Review
Thermal stress has a direct effect on various types of DNA damage, which depends on the stage of the cell cycle when the cell is exposed to different climate conditions. A literature review was conducted to systematically investigate and assess the overall effect of heat stress and DNA damage following heat exposure. In this study, electronic databases including PubMed, Scopus, and Web of Science were searched to find relevant literature on DNA damage in different ambient temperatures. Outcomes included (1) measurement of DNA damage in heat exposure, (2) three different quantification methods (comet assay, 8-hydroxy-2-deoxyguanosine (8-OHdG), and γ-H2AX), and (3) protocols used for moderate (31) and high temperatures (42). The evidence shows that long exposure and very high temperature can induce an increase in DNA damage through aggregate in natural proteins, ROS generation, cell death, and reproductive damage in hot-humid and hot-dry climate conditions. A substantial increase in DNA damage occurs following acute heat stress exposure, especially in tropical and subtropical climate conditions. The results of this systematic literature review showed a positive association between thermal stress exposure and inhibition of repair of DNA damage.
Topics: Humans; DNA Damage; 8-Hydroxy-2'-Deoxyguanosine; Heat Stress Disorders; Heat-Shock Response; Hot Temperature
PubMed: 36178536
DOI: 10.1007/s00484-022-02351-w -
Medicine Apr 2023O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that maintains the stability of genetic information. MGMT is a strong prognostic biomarker in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that maintains the stability of genetic information. MGMT is a strong prognostic biomarker in patients with glioblastoma. However, the effect of its gene hypermethylation and expression on the survival rate of head and neck cancer (HNC) patients is still disputed. Therefore, we conducted a meta-analysis to evaluate the prognostic value of MGMT hypermethylation and expression in HNC patients.
METHODS
This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and was registered at the International Prospective Register of Systematic Reviews (CRD42021274728). Literature related to the survival rate of HNC patients and MGMT was systematically searched in PubMed, Embase, The Cochrane Library and Web of Science electronic databases (published from inception to February 1, 2023). The association was evaluated by the combined hazard ratio (HR) and related 95% confidence interval (CI). Two authors independently screened all records and extracted the data. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation system. All of the statistical tests used in this meta-analysis were conducted with Stata 12.0 software.
RESULTS
We included 5 studies with 564 HNC patients for the meta-analysis. All of the included patients were primary tumors and underwent surgical resection without prior radiotherapy or chemotherapy therapy. No significant heterogeneity was noted between MGMT and overall survival, MGMT and disease-free survival, and a fixed-effects model was used. HNC patients with MGMT hypermethylation and low expression had a poor prognosis, with pooled HR for overall survival (HR = 1.23, 95% CI: 1.10-1.38, P < .001) and disease-free survival (HR = 2.28, 95% CI: 1.45-3.58, P < .001). Subgroup analysis stratified by molecular abnormalities, such as hypermethylation or low expression, showed similar results. The insufficient number of trials included in our study encountered high risk of bias and may increase the deviation of the final meta-analysis results.
CONCLUSION
HNC patients with MGMT hypermethylation and low expression were more likely to exhibit poorer survival. MGMT hypermethylation and low expression can predict survival in patients with HNC.
Topics: Humans; Prognosis; DNA Methylation; O(6)-Methylguanine-DNA Methyltransferase; DNA Repair Enzymes; Head and Neck Neoplasms; DNA
PubMed: 37026932
DOI: 10.1097/MD.0000000000033472 -
Iranian Journal of Cancer Prevention Feb 2016Known polymorphisms of DNA repair genes can be associated with the risk of many types of cancer. There is no consensus regarding association between XRCC1 and OGG1 with... (Review)
Review
CONTEXT
Known polymorphisms of DNA repair genes can be associated with the risk of many types of cancer. There is no consensus regarding association between XRCC1 and OGG1 with breast cancer (BC).
OBJECTIVES
The aim of this study is to collect relevant published studies systematically.
DATA SOURCES
Sixty-two publications were identified through searching PubMed, PubMed Central, ISI web of knowledge, and reference list of related articles.
STUDY SELECTION
We performed a systematic review according MOOSE guideline criteria. All longitudinal cohort and case-control studies investigating association of any type and grade of breast cancer with XRCC1 and OGG1 gene and their polymorphisms were eligible for initial inclusion.
DATA EXTRACTION
Two authors screened titles and abstracts and extracted all needed information from eligible studies. Four research methodological components causing bias for the association between gene polymorphisms and breast cancer risk, including source of controls sampling, population ethnicity, sample size of studies and menopausal status of cases and controls was used for assessment of quality of studies.
RESULTS
A total of 14,793 breast cancer cases and 15,409 controls were included in assessment of XRCC1 Arg194Trp. Four studies showed significant association and one study showed protective effect of XRCC1 Arg194Trp and BC. A total of 7,716 cases and 7,370 controls were included for XRCC1 Arg280His. Only one study showed significant association of XRCC1 Arg280His and breast cancer (OR = 1.82 (1.06 - 3.15). A total of 27,167 cases and 31,998 controls were included to estimate association between XRCC1 Arg399Gln polymorphism and breast cancer. Seven studies showed significant association and one showed protective effect of XRCC1 Arg399Gln and BC. A total of 9,417 cases and 11,087 controls were included for OGG1 Ser326Cys. Among studies focused on OGG1 Ser326Cys, none showed significant association with breast cancer.
CONCLUSIONS
Systematic search of major databases identify many studies addressing the relationship between BC and susceptible alleles in the base excision repair genes and the fact that there are many variations in the magnitude of association depending on inheritance model and the population of the study.
PubMed: 27366307
DOI: 10.17795/ijcp-3467 -
Reports of Practical Oncology and... 2022Exposure to the same environmental factors in different people have resulted in different susceptibility to head and neck squamous cell carcinoma (HNSCC), which suggests... (Review)
Review
BACKGROUND
Exposure to the same environmental factors in different people have resulted in different susceptibility to head and neck squamous cell carcinoma (HNSCC), which suggests genetic variation may be a risk factor for the development of HNSCC. So, the aim was to review literatures on the association between gene polymorphisms and risk of HNSCCs.
MATERIALS AND METHODS
This systematic review included all articles on the impact of gene polymorphisms on risk and susceptibility to HNSCC published till September 2021 using PubMed, Web of science, SCOPUS, Google Scholar and Cochrane library databases.
RESULTS
Of 1163 initial searched articles, 77 articles were eligible to include in this review. Studies were categorized based on gene functions. In each category, studied gene polymorphisms related to growth control genes, cell cycle control, apoptosis, DNA repair genes, carcinogen-metabolizing enzymes, alcohol-metabolizing genes, antioxidant gene, inflammatory cytokine, transcription factor, tumor immunity, folate metabolism, and tumor suppressor gene were discussed separately. Among the polymorphisms that are often significantly associated with HNSCC risk are: null, null, *4, Arg194Trp and Arg399Gln, C8092A, Lys751Gln, Thr241Met, codon 72 and C677T polymorphisms.
CONCLUSION
Varied and contradictory results have been reported in different studies regarding the association of gene polymorphisms with HNSCC risk. To conclude about this association and to overcome these contradictions, it is necessary to use the results of existing meta-analyses or to perform new or updated meta-analyses.
PubMed: 36632298
DOI: 10.5603/RPOR.a2022.0115 -
Cancer Treatment Reviews Nov 2023PARP inhibitors (PARPi) are a standard-of-care (SoC) treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). Several clinical trials... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
PARP inhibitors (PARPi) are a standard-of-care (SoC) treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). Several clinical trials have shown the potential of combining PARPi with other anticancer agents. Therefore, we conducted a systematic review and meta-analysis to comprehensively evaluate the efficacy and safety of PARPi in patients with metastatic prostate cancer.
METHODS
MEDLINE, Cochrane CENTRAL, EMBASE, CINAHL, and Web of Science were searched on March 22nd, 2023, for phase 2 or 3 clinical trials. Efficacy (progression-free survival [PFS], overall survival [OS], PSA decline >50% [PSA50], and objective response rate [ORR]) and safety outcomes were assessed in the included studies.
RESULTS
Seventeen clinical trials (PARPi monotherapy [n = 7], PARPi + androgen-receptor signaling inhibitors [ARSI] [n = 6], and PARPi + immune checkpoint inhibitors [ICI] [n = 4]) were included in the quantitative analyses. PARPi monotherapy improved radiographic PFS and OS over SoC in mCRPC patients with alterations in BRCA1 or BRCA2 genes but not in those with alterations in the ATM gene. Higher rates of PSA50 and ORR were reported in participants treated with PARPi + ARSI than in single-agent PARPi or PARPi + ICI. Although the rate of high-grade adverse events was similar across all groups, treatment discontinuation was higher in patients treated with PARPi-based combinations than PARPi monotherapy.
CONCLUSION
The efficacy of PARPi is not uniform across mCRPC patients with alterations in DNA damage repair genes, and optimal patient selection remains a clinical challenge. No unexpected safety signals for this class of agents emerged from this analysis.
Topics: Male; Humans; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms, Castration-Resistant; Immune Checkpoint Inhibitors; Patient Selection; Progression-Free Survival
PubMed: 37716332
DOI: 10.1016/j.ctrv.2023.102623 -
Human Reproduction Update Jan 2020Endometriosis is an estrogen-dependent gynecological disorder that affects at least 10% of women of reproductive age. It may lead to infertility and non-specific... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Endometriosis is an estrogen-dependent gynecological disorder that affects at least 10% of women of reproductive age. It may lead to infertility and non-specific symptoms such as chronic pelvic pain. Endometriosis screening and diagnosis are difficult and time-consuming. Late diagnosis (with a delay ranging from 3.3 to 10.7 years) is a major problem and may contribute to disease progression and a worse response to treatment once initiated. Efficient screening tests might reduce this diagnostic delay. As endometriosis is presumed to be a complex disease with several genetic and non-genetic pathogenic factors, many researchers have sought to identify polymorphisms that predispose to this condition.
OBJECTIVE AND RATIONALE
We performed a systematic review and meta-analysis of the most regularly reported polymorphisms in order to identify those that might predispose to endometriosis and might thus be of value in screening.
SEARCH METHODS
The MEDLINE database was searched for English-language publications on DNA polymorphisms in endometriosis, with no date restriction. The PubTator text mining tool was used to extract gene names from the selected publications' abstracts. We only selected polymorphisms reported by at least three studies, having applied strict inclusion and exclusion criteria to their control populations. No stratification based on ethnicity was performed. All steps were carried out according to PRISMA guidelines.
OUTCOMES
The initial selection of 395 publications cited 242 different genes. Sixty-two genes (corresponding to 265 different polymorphisms) were cited at least in three publications. After the application of our other selection criteria (an original case-control study of endometriosis, a reported association between endometriosis and at least one polymorphism, data on women of reproductive age and a diagnosis of endometriosis in the cases established by surgery and/or MRI and confirmed by histology), 28 polymorphisms were eligible for meta-analysis. Only five of the 28 polymorphisms were found to be significantly associated with endometriosis: interferon gamma (IFNG) (CA) repeat, glutathione S-transferase mu 1 (GSTM1) null genotype, glutathione S-transferase pi 1 (GSTP1) rs1695 and wingless-type MMTV integration site family member 4 (WNT4) rs16826658 and rs2235529. Six others showed a significant trend towards an association: progesterone receptor (PGR) PROGINS, interCellular adhesion molecule 1 (ICAM1) rs1799969, aryl-hydrocarbon receptor repressor (AHRR) rs2292596, cytochrome family 17 subfamily A polypeptide 1 (CYP17A1) rs743572, CYP2C19 rs4244285 and peroxisome proliferator-activated receptor gamma (PPARG) rs1801282), and 12 showed a significant trend towards the lack of an association: tumor necrosis factor (TNF) rs1799964, interleukin 6 (IL6) rs1800796, transforming growth factor beta 1 (TGFB1) rs1800469, estrogen receptor 1 (ESR1) rs2234693, PGR rs10895068, FSH receptor (FSHR) rs6166, ICAM1 rs5498, CYP1A1 rs4646903, CYP19A1 rs10046, tumor protein 53 (TP53) rs1042522, X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) rs25487 and serpin peptidase inhibitor clade E member 1 (SERPINE1) rs1799889; however, for the 18 polymorphisms identified in the latter two groups, further studies of the potential association with the endometriosis risk are needed. The remaining five of the 28 polymorphisms were not associated with endometriosis: glutathione S-transferase theta 1 (GSTT1) null genotype, vascular endothelial growth factor alpha (VEGFA) rs699947, rs833061, rs2010963 and rs3025039.
WIDER IMPLICATIONS
By carefully taking account of how the control populations were defined, we identified polymorphisms that might be candidates for use in endometriosis screening and polymorphisms not associated with endometriosis. This might constitute the first step towards identifying polymorphism combinations that predispose to endometriosis (IFNG (CA) repeat, GSTM1 null genotype, GSTP1 rs1695, WNT4 rs16826658 and WNT4 rs2235529) in a large cohort of patients with well-defined inclusion criteria. In turn, these results might improve the diagnosis of endometriosis in primary care. Lastly, our present findings may enable a better understanding of endometriosis and improve the management of patients with this disease.
Topics: Aromatase; Case-Control Studies; Cytochrome P-450 CYP1A1; Early Diagnosis; Endometriosis; Female; Genetic Predisposition to Disease; Genotype; Glutathione S-Transferase pi; Glutathione Transferase; Humans; Interferon-gamma; Mass Screening; Polymorphism, Genetic; Vascular Endothelial Growth Factor A; Wnt4 Protein
PubMed: 31821471
DOI: 10.1093/humupd/dmz034 -
Cancer Chemotherapy and Pharmacology Nov 2021Melphalan is a bifunctional alkylating agent that elicits its cytotoxic activity by rapidly forming an initial DNA monoadduct, which then produces an inter-strand...
PURPOSE
Melphalan is a bifunctional alkylating agent that elicits its cytotoxic activity by rapidly forming an initial DNA monoadduct, which then produces an inter-strand crosslink. Most studies exploring the role of inherited differences in DNA repair and melphalan outcomes focus on inter-strand crosslink repair, however, monoadduct repair likely plays a key role since it minimises the ultimate production of these crosslinks. The purpose of this systematic review was to assess evidence of an association between variation in monoadduct repair pathways and melphalan response.
METHODS
A literature search was undertaken using Medline, Embase, Scopus and PubMed databases. Duplicates were removed and only full-text articles were included. To be included for critique in this systematic review, articles were assessed for relevance using strict inclusion/exclusion criteria.
RESULTS
Fourteen studies were identified that involved patients treated with melphalan, however, in 3, only a minority of the cohort received melphalan. Across the remaining 11 studies, 61 genes/proteins in DNA monoadduct repair pathways were assessed. Both germline SNP (CDKN1A, ERCC1, ERCC2, ERCC4, ERCC6, EXO1, MLH1, MNAT1, MUTYH, PARP4, PCNA, POLE, POLR1G, RAD23B, RFC1, RFC3, RPA1, RPA3, TREX1, UNG, XPC, XRCC1) and somatic expression (CDKN1A, PARP1, PCNA, MGMT, RECQL, RFC5) were associated with melphalan outcomes in ≥ 1 study.
CONCLUSION
It appears that inherited germline differences in monoadduct repair genes may be a risk factor for poor outcomes. However, the diversity of study design, patient cohorts, genes assessed and lack of replication, preclude any meta-analysis. Further prospective studies are required to validate these findings.
Topics: Antineoplastic Agents, Alkylating; DNA Adducts; DNA Repair; Gene Expression Regulation, Neoplastic; Humans; Melphalan; Neoplasms; Pharmacogenomic Variants; Progression-Free Survival; Treatment Outcome
PubMed: 34347127
DOI: 10.1007/s00280-021-04340-z -
Human & Experimental Toxicology Oct 2012Genetic variation in DNA repair genes can modulate DNA repair capacity and may be related to cancer risk. However, study findings have been inconsistent. Inheritance of... (Review)
Review
Genetic variation in DNA repair genes can modulate DNA repair capacity and may be related to cancer risk. However, study findings have been inconsistent. Inheritance of variant DNA repair genes is believed to influence individual susceptibility to the development of environmental cancer. Reliable knowledge on which the base excision repair (BER) sequence variants are associated with cancer risk would help elucidate the mechanism of cancer. Given that most of the previous studies had inadequate statistical power, we have conducted a systematic review on sequence variants in three important BER proteins. Here, we review published studies on the association between polymorphism in candidate BER genes and cancer risk. We focused on three key BER genes: 8-oxoguanine DNA glycosylase (OGG1), apurinic/apyrimidinic endonuclease (APE1/APEX1) and x-ray repair cross-complementing group 1 (XRCC1). These specific DNA repair genes were selected because of their critical role in maintaining genome integrity and, based on previous studies, suggesting that single-nucleotide polymorphisms (SNPs) in these genes have protective or deleterious effects on cancer risk. A total of 136 articles in the December 13, 2010 MEDLINE database (National Center for Biotechnology Information, http://www.ncbi.nlm.nih.gov/pubmed/) reporting polymorphism in OGG1, XRCC1 or APE1 genes were analyzed. Many of the reported SNPs had diverse association with specific human cancers. For example, there was a positive association between the OGG1 Ser326Cys variant and gastric and lung cancer, while the XRCC1 Arg399Gln variant was associated with reduced cancer risk. Gene-environment interactions have been noted and may be important for colorectal and lung cancer risk and possibly other human cancers.
Topics: Animals; DNA Glycosylases; DNA Repair; DNA Repair Enzymes; DNA-(Apurinic or Apyrimidinic Site) Lyase; DNA-Binding Proteins; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Neoplasms; Odds Ratio; Phenotype; Polymorphism, Single Nucleotide; Risk Assessment; Risk Factors; X-ray Repair Cross Complementing Protein 1
PubMed: 23023028
DOI: 10.1177/0960327112444476 -
Molecular Biotechnology Apr 2022The CRISPR-Cas genome editing system is an intrinsic property of a bacteria-based immune system. This employs a guide RNA to detect and cleave the PAM-associated target... (Review)
Review
The CRISPR-Cas genome editing system is an intrinsic property of a bacteria-based immune system. This employs a guide RNA to detect and cleave the PAM-associated target DNA or RNA in subsequent infections, by the invasion of a similar bacteriophage. The discovery of Cas systems has paved the way to overcome the limitations of existing genome editing tools. In this review, we focus on Cas proteins that are available for gene modifications among which Cas9, Cas12a, and Cas13 have been widely used in the areas of medicine, research, and diagnostics. Since CRISPR has been already proven for its potential research applications, the next milestone for CRISPR will be proving its efficacy and safety. In this connection, we systematically review recent advances in exploring multiple variants of Cas proteins and their modifications for therapeutic applications.
Topics: CRISPR-Cas Systems; DNA; Gene Editing; RNA; RNA, Guide, CRISPR-Cas Systems
PubMed: 34741732
DOI: 10.1007/s12033-021-00422-8 -
Contemporary Oncology (Poznan, Poland) 2021Anaplastic thyroid carcinoma is a rare, rapidly progressing, highly aggressive thyroid malignancy. Responses to immune checkpoint inhibitors in mismatch... (Review)
Review
INTRODUCTION
Anaplastic thyroid carcinoma is a rare, rapidly progressing, highly aggressive thyroid malignancy. Responses to immune checkpoint inhibitors in mismatch repair-deficient/microsatellite instability-high tumours of other locations have shown promising results, and with the extended approval of the PD-1 receptor inhibitor pembrolizumab by the Food and Drug Administration, also anaplastic thyroid cancer (ATC) requires analysis for microsatellite instability (MSI) status.
MATERIAL AND METHODS
Systematic research for relevant literature was conducted in different databases. Prevalence, detection methods, and the potential prognostic/predictive value of MSI in view of the available targeted therapies were of special focus.
RESULTS
Selected citations revealed the prevalence of MSI in 7.4%, with mutations in the MSH2 gene (33%) being the most frequent, followed by MSH6 (25%) and MLH1 (16.7%) occurring in the following combinations: MLH1-MSH2 (8.3%), MSH2-MSH6 (8.3%), and MLH3-MSH5 (8.3%). No mutations in the PMS2 gene were reported. Sixty-six co-mutations in 9 cases were found, with TP53 (88.9%), NF1 (44.4 %), ATM (33.3%), and RB1 (33.3%) being the most frequent. No RAS mutations were noted. Survival ranged between 2.8 and 48 months, and patient age varied between 49 and 84 years. There are insufficient and heterogenous data concerning the predictive or prognostic value of mismatch repair-deficient/microsatellite instability status.
CONCLUSIONS
Tumour molecular profiling is fundamental in ATC for predictive, prognostic, as well as therapeutic reasons, and analysis of MSI status is strongly suggested because a small subgroup show the MSI signature and might profit from recently approved targeted therapies.
PubMed: 34729042
DOI: 10.5114/wo.2021.110052