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1
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Ornos ED, Cando LF, Catral CD, Quebral EP, Tantengco OA, Arevalo MVP, Dee EC. Molecular basis of sex differences in cancer: Perspective from Asia. iScience 2023; 26:107101. [PMID: 37404373 PMCID: PMC10316661 DOI: 10.1016/j.isci.2023.107101] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/06/2023] Open
Abstract
Cancer is a leading cause of mortality and morbidity globally. Sex differences in cancer are evident in death rates and treatment responses in several cancers. Asian patients have unique cancer epidemiology influenced by their genetic ancestry and sociocultural factors in the region. In this review, we show molecular associations that potentially mediate sex disparities observed in cancer in Asian populations. Differences in sex characteristics are evident at the cytogenetic, genetic, and epigenetic levels mediating processes that include cell cycle, oncogenesis, and metastasis. Larger clinical and in vitro studies that explore mechanisms can confirm the associations of these molecular markers. In-depth studies of these markers can reveal their importance as diagnostics, prognostics, and therapeutic efficacy markers. Sex differences should be considered in designing novel cancer therapeutics in this era of precision medicine.
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Affiliation(s)
- Eric David Ornos
- Department of Medical Microbiology, College of Public Health, University of the Philippines Manila, Manila 1000, Philippines
- College of Medicine, University of the Philippines Manila, Manila, 1000, Philippines
| | - Leslie Faye Cando
- College of Medicine, University of the Philippines Manila, Manila, 1000, Philippines
| | | | - Elgin Paul Quebral
- College of Medicine, University of the Philippines Manila, Manila, 1000, Philippines
- Virology Laboratory, Department of Medical Microbiology, College of Public Health, University of the Philippines Manila, Manila 1000, Philippines
- Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA
| | - Ourlad Alzeus Tantengco
- College of Medicine, University of the Philippines Manila, Manila, 1000, Philippines
- Department of Physiology, College of Medicine, University of the Philippines Manila, Manila 1000, Philippines
- Department of Biology, College of Science, De La Salle University, Manila 0922, Philippines
| | | | - Edward Christopher Dee
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10028, USA
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2
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Miner KM, Jamenis AS, Bhatia TN, Clark RN, Rajasundaram D, Sauvaigo S, Mason DM, Posimo JM, Abraham N, DeMarco BA, Hu X, Stetler RA, Chen J, Sanders LH, Luk KC, Leak RK. α-synucleinopathy exerts sex-dimorphic effects on the multipurpose DNA repair/redox protein APE1 in mice and humans. Prog Neurobiol 2022; 216:102307. [PMID: 35710046 PMCID: PMC9514220 DOI: 10.1016/j.pneurobio.2022.102307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 04/05/2022] [Accepted: 06/10/2022] [Indexed: 11/16/2022]
Abstract
Lewy body disorders are characterized by oxidative damage to DNA and inclusions rich in aggregated forms of α-synuclein. Among other roles, apurinic/apyrimidinic endonuclease 1 (APE1) repairs oxidative DNA damage, and APE1 polymorphisms have been linked to cases of Lewy body disorders. However, the link between APE1 and α-synuclein is unexplored. We report that knockdown or inhibition of APE1 amplified inclusion formation in primary hippocampal cultures challenged with preformed α-synuclein fibrils. Fibril infusions into the mouse olfactory bulb/anterior olfactory nucleus (OB/AON) elicited a modest decrease in APE1 expression in the brains of male mice but an increase in females. Similarly, men with Lewy body disorders displayed lower APE1 expression in the OB and amygdala compared to women. Preformed fibril infusions of the mouse OB/AON induced more robust base excision repair of DNA lesions in females than males. No fibril-mediated loss of APE1 expression was observed in male mice when the antioxidant N-acetylcysteine was added to their diet. These findings reveal a potential sex-biased link between α-synucleinopathy and APE1 in mice and humans. Further studies are warranted to determine how this multifunctional protein modifies α-synuclein inclusions and, conversely, how α-synucleinopathy and biological sex interact to modify APE1.
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Affiliation(s)
- Kristin M Miner
- Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA
| | - Anuj S Jamenis
- Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA
| | - Tarun N Bhatia
- Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA
| | - Rachel N Clark
- Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA
| | - Dhivyaa Rajasundaram
- Department of Pediatrics, Rangos Research Center, UPMC Children's Hospital of Pittsburgh, PA 15224, USA
| | | | - Daniel M Mason
- Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA
| | - Jessica M Posimo
- Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA
| | - Nevil Abraham
- Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA
| | - Brett A DeMarco
- Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA
| | - Xiaoming Hu
- Department of Neurology, University of Pittsburgh, PA 15213, USA
| | - R Anne Stetler
- Department of Neurology, University of Pittsburgh, PA 15213, USA
| | - Jun Chen
- Department of Neurology, University of Pittsburgh, PA 15213, USA
| | - Laurie H Sanders
- Department of Neurology, Duke University School of Medicine, Durham, NC 27710, USA
| | - Kelvin C Luk
- Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19147, USA
| | - Rehana K Leak
- Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA.
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3
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Garcia FADO, de Andrade ES, de Campos Reis Galvão H, da Silva Sábato C, Campacci N, de Paula AE, Evangelista AF, Santana IVV, Melendez ME, Reis RM, Palmero EI. New insights on familial colorectal cancer type X syndrome. Sci Rep 2022; 12:2846. [PMID: 35181726 PMCID: PMC8857274 DOI: 10.1038/s41598-022-06782-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 12/17/2021] [Indexed: 12/22/2022] Open
Abstract
Familial colorectal cancer type X (FCCTX) is a heterogeneous colorectal cancer predisposition syndrome that, although displays a cancer pattern similar to Lynch syndrome, is mismatch repair proficient and does not exhibit microsatellite instability. Besides, its genetic etiology remains to be elucidated. In this study we performed germline exome sequencing of 39 cancer-affected patients from 34 families at risk for FCCTX. Variant classification followed the American College of Medical Genetics and Genomics (ACMG) guidelines. Pathogenic/likely pathogenic variants were identified in 17.65% of the families. Rare and potentially pathogenic alterations were identified in known hereditary cancer genes (CHEK2), in putative FCCTX candidate genes (OGG1 and FAN1) and in other cancer-related genes such as ATR, ASXL1, PARK2, SLX4 and TREX1. This study provides novel important clues that can contribute to the understanding of FCCTX genetic basis.
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Affiliation(s)
- Felipe Antonio de Oliveira Garcia
- Molecular Oncology Research Center, Barretos Cancer Hospital, Antenor Duarte Villela Street, 1331, Barretos, São Paulo, CEP 14784-400, Brazil
| | - Edilene Santos de Andrade
- Molecular Oncology Research Center, Barretos Cancer Hospital, Antenor Duarte Villela Street, 1331, Barretos, São Paulo, CEP 14784-400, Brazil
| | | | | | - Natália Campacci
- Molecular Oncology Research Center, Barretos Cancer Hospital, Antenor Duarte Villela Street, 1331, Barretos, São Paulo, CEP 14784-400, Brazil
| | | | - Adriane Feijó Evangelista
- Molecular Oncology Research Center, Barretos Cancer Hospital, Antenor Duarte Villela Street, 1331, Barretos, São Paulo, CEP 14784-400, Brazil
| | | | - Matias Eliseo Melendez
- Molecular Oncology Research Center, Barretos Cancer Hospital, Antenor Duarte Villela Street, 1331, Barretos, São Paulo, CEP 14784-400, Brazil.,Department of Molecular Carcinogenesis, Brazilian National Cancer Institute, Rio de Janeiro, Brazil
| | - Rui Manuel Reis
- Molecular Oncology Research Center, Barretos Cancer Hospital, Antenor Duarte Villela Street, 1331, Barretos, São Paulo, CEP 14784-400, Brazil.,Center of Molecular Diagnosis, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.,Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, Braga, Portugal.,ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Edenir Inez Palmero
- Molecular Oncology Research Center, Barretos Cancer Hospital, Antenor Duarte Villela Street, 1331, Barretos, São Paulo, CEP 14784-400, Brazil. .,Department of Genetics, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.
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Malfatti MC, Antoniali G, Codrich M, Burra S, Mangiapane G, Dalla E, Tell G. New perspectives in cancer biology from a study of canonical and non-canonical functions of base excision repair proteins with a focus on early steps. Mutagenesis 2021; 35:129-149. [PMID: 31858150 DOI: 10.1093/mutage/gez051] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Accepted: 12/05/2019] [Indexed: 12/15/2022] Open
Abstract
Alterations of DNA repair enzymes and consequential triggering of aberrant DNA damage response (DDR) pathways are thought to play a pivotal role in genomic instabilities associated with cancer development, and are further thought to be important predictive biomarkers for therapy using the synthetic lethality paradigm. However, novel unpredicted perspectives are emerging from the identification of several non-canonical roles of DNA repair enzymes, particularly in gene expression regulation, by different molecular mechanisms, such as (i) non-coding RNA regulation of tumour suppressors, (ii) epigenetic and transcriptional regulation of genes involved in genotoxic responses and (iii) paracrine effects of secreted DNA repair enzymes triggering the cell senescence phenotype. The base excision repair (BER) pathway, canonically involved in the repair of non-distorting DNA lesions generated by oxidative stress, ionising radiation, alkylation damage and spontaneous or enzymatic deamination of nucleotide bases, represents a paradigm for the multifaceted roles of complex DDR in human cells. This review will focus on what is known about the canonical and non-canonical functions of BER enzymes related to cancer development, highlighting novel opportunities to understand the biology of cancer and representing future perspectives for designing new anticancer strategies. We will specifically focus on APE1 as an example of a pleiotropic and multifunctional BER protein.
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Affiliation(s)
- Matilde Clarissa Malfatti
- Laboratory of Molecular Biology and DNA repair, Department of Medicine (DAME), University of Udine, Udine, Italy
| | - Giulia Antoniali
- Laboratory of Molecular Biology and DNA repair, Department of Medicine (DAME), University of Udine, Udine, Italy
| | - Marta Codrich
- Laboratory of Molecular Biology and DNA repair, Department of Medicine (DAME), University of Udine, Udine, Italy
| | - Silvia Burra
- Laboratory of Molecular Biology and DNA repair, Department of Medicine (DAME), University of Udine, Udine, Italy
| | - Giovanna Mangiapane
- Laboratory of Molecular Biology and DNA repair, Department of Medicine (DAME), University of Udine, Udine, Italy
| | - Emiliano Dalla
- Laboratory of Molecular Biology and DNA repair, Department of Medicine (DAME), University of Udine, Udine, Italy
| | - Gianluca Tell
- Laboratory of Molecular Biology and DNA repair, Department of Medicine (DAME), University of Udine, Udine, Italy
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5
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Nigam K, Yadav SK, Sanyal S. XRCC1 A>G polymorphism, smoking and the risk of squamous cell carcinoma of the head and neck. GENE REPORTS 2020. [DOI: 10.1016/j.genrep.2020.100838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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6
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Association between apurinic/apyrimidinic endonuclease 1 rs1760944 T>G polymorphism and susceptibility of cancer: a meta-analysis involving 21764 subjects. Biosci Rep 2020; 39:221420. [PMID: 31804681 PMCID: PMC6923335 DOI: 10.1042/bsr20190866] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2019] [Revised: 10/03/2019] [Accepted: 12/04/2019] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Previous case-control studies have suggested that apurinic/apyrimidinic endonuclease 1 (APE1) rs1760944 T>G polymorphism may be associated with cancer risk. Here, we carried out an updated meta-analysis to focus on the correlation between APE1 rs1760944 T>G locus and the risk of cancer. METHODS We used the crude odds ratios (ORs) with their 95% confidence intervals (CIs) to evaluate the possible relationship between the APE1 rs1760944 T>G polymorphism and cancer risk. Heterogeneity, publication bias and sensitivity analysis were also harnessed to check the potential bias of the present study. RESULTS Twenty-three independent studies involving 10166 cancer cases and 11598 controls were eligible for this pooled analysis. We found that APE1 rs1760944 T>G polymorphism decreased the risk of cancer in four genetic models (G vs. T: OR, 0.87; 95% CI, 0.83-0.92; P<0.001; GG vs. TT: OR, 0.77; 95% CI, 0.69-0.86; P<0.001; GG/TG vs. TT: OR, 0.83; 95% CI, 0.77-0.89, P<0.001 and GG vs. TT/TG: OR, 0.85; 95% CI, 0.80-0.92, P<0.001). Results of subgroup analyses also demonstrated that this single-nucleotide polymorphism (SNP) modified the risk among lung cancer, breast cancer, osteosarcoma, and Asians. Evidence of publication bias was found in the present study. When we treated the publication bias with 'trim-and-fill' method, the adjusted ORs and CIs were not significantly changed. CONCLUSION In conclusion, current evidence highlights that the APE1 rs1760944 T>G polymorphism is a protective factor for cancer susceptibility. In the future, case-control studies with detailed risk factors are needed to confirm or refute our findings.
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Ghelmani Y, Asadian F, Antikchi MH, Dastgheib SA, Shaker SH, Jafari-Nedooshan J, Neamatzadeh H. Association Between the hOGG1 1245C>G (rs1052133) Polymorphism and Susceptibility to Colorectal Cancer: a Meta-analysis Based on 7010 Cases and 10,674 Controls. J Gastrointest Cancer 2020; 52:389-398. [PMID: 33025423 DOI: 10.1007/s12029-020-00532-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/27/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND The 1245C>G (rs1052133) polymorphism of human 8-oxoguanine DNA glycosylase 1 (hOGG1) gene has been indicated to be correlated with colorectal (CRC) susceptibility, but studies have yielded conflicting results. Thus, the present meta-analysis was performed to derive a more precise estimation between hOGG1 1245C>G polymorphism and CRC risk. METHODS Data were collected from several electronic databases such as PubMed, EMBASE, and Google Scholar databases, with the last search up to September 01, 2020. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to assess the strength of the association. RESULTS A total of 24 case-control studies with 7010 CRC cases and 10,674 controls were selected. Pooled data showed that the hOGG1 1245C>G polymorphism was significantly associated with CRC risk under three genetic models, i.e., homozygote (GG vs. CC: OR = 1.229, 95% CI 1.031-1.465, p = 0.022); heterozygote (GC vs. CC: OR = 1.142, 95% CI 1.008-1.294, p = 0.037); and dominant (GG+GC vs. CC: OR = 1.162, 95% CI 1.034-1.304, p = 0.011). When stratified analysis by ethnicity, a significant association of the hOGG1 1245C>G polymorphism with risk of CRC was found in the Caucasians, but not in Asians. Moreover, there were significant associations between hOGG1 1245C>G polymorphism and CRC by PCR-RFLP and hospital-based subgroups. CONCLUSIONS Inconsistent with the previous meta-analysis, these meta-analysis results revealed that the hOGG1 1245C>G polymorphism might be associated with an increased risk of CRC, especially in Caucasians.
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Affiliation(s)
- Yaser Ghelmani
- Clinical Research Development Center of Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Fatemeh Asadian
- Department of Medical Laboratory Sciences, School of Paramedical Science, Shiraz University of Medical Sciences, Shiraz, Iran.
| | | | - Seyed Alireza Dastgheib
- Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Hossein Shaker
- Department of Emergency Medicine, Iran University of Medical Sciences, Tehran, Iran
| | | | - Hossein Neamatzadeh
- Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Mother and Newborn Health Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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8
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Hosseini SM, Mohammadiasl J, Talaiezadeh A, Alidadi R, Bijanzadeh M. Influence of Two DNA Repair Pathway Polymorphisms in Colorectal Cancer Risk in Southwest Iran. Asian Pac J Cancer Prev 2020; 21:1919-1924. [PMID: 32711416 PMCID: PMC7573413 DOI: 10.31557/apjcp.2020.21.7.1919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Indexed: 11/25/2022] Open
Abstract
Objective: X-ray cross-complementing group 1 (XRCC1) and 8 Oxo guanine DNA-glycosylase 1 (OGG1) genes are implicated in the repair of single-stranded breaks (SSBRs) and base excision repair (BER) pathways. Common polymorphisms in DNA repair genes are supposed to decrease the capability of DNA repair and cause genetic instability. This study was designed to investigate the association between XRCC1 (rs25487) and OGG1 (rs1052133) polymorphisms and susceptibility to colorectal cancer (CRC) in the Ahvaz city, south-west Iran. Methods: This case- control study comprised 150 patients and 150 controls that were selected from 2 educational hospitals in Ahvaz. They were matched for age and gender, and their genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: Our results indicate that the frequency of the Gln (A) allele of XRCC1 (rs25487) is significantly higher in colorectal cancer patients, compare to controls (p = 0.01, OR: 1.54, 95% CI 1.9–13.3). Significant increased risk of cancer was observed in XRCC1 (rs25487) genotypes (p = 0.001 OR: 5.3, 95% CI 1.9–14.2 for Gln / Gln), while no association was found between OGG1 (rs1052133) and colorectal cancer risk (p = 0.6). Conclusion: Our study suggests that XRCC1 (rs25487) polymorphism might be associated with an increasing risk of CRC in Ahvaz. It also demonstrates positive correlation between the XRCC1 (rs25487) genotypes and demographic characteristics, such as smoking and increased age in patients and control groups.
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Affiliation(s)
- Seyed Mohammad Hosseini
- Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Javad Mohammadiasl
- Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Abdulhasan Talaiezadeh
- Cancer, Environmental and Petroleum Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Department of General Surgery, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Rahim Alidadi
- Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mahdi Bijanzadeh
- Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Cancer, Environmental and Petroleum Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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9
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Kudhair BK, Alabid NN, Zayed KS, Lafta IJ, Taheri-Kafrani A. The correlation of combined OGG1, CYP1A1 and GSTP1 gene variants and risk of lung cancer of male Iraqi waterpipe tobacco smokers. Mol Biol Rep 2020; 47:5155-5163. [PMID: 32577993 DOI: 10.1007/s11033-020-05589-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 06/11/2020] [Indexed: 12/12/2022]
Abstract
Genetic polymorphisms of genes whose products are responsible for activities, such as xenobiotic metabolism, mutagen detoxification and DNA-repair, have been predicted to be associated with the risk of developing lung cancer (LC). The association of LC with tobacco smoking has been extensively investigated, but no studies have focused on the Arab ethnicity. Previously, we examined the association between genetic polymorphisms among Phase I and Phase II metabolism genes and the risk of LC. Here, we extend the data by examining the correlation of OGG1 Ser326Cys combined with CYP1A1 (Ile462Val and MspI) and GSTP1 (Ile105Val and Ala103Val) polymorphisms with the risk of LC. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and gene sequencing were carried out for genotyping the OGG1 polymorphisms of 123 LC patients and 129 controls. No significant differences in the frequencies of the OGG1 mutant allele between patients and controls were found. The distributions of heterozygous Ser/Cys or Cys/Cys genotypes of OGG1 were not associated with the risk of LC either according to the histological types of LC or based on waterpipe tobacco (WP) smoking status. In contrast, the combined effect of OGG1 variants with CYP1A1 and GSTP1 variants revealed a significant correlation with the OGG1 Ser326Cys-CYP1A1 MspI variants pairing. This association was significant (p = 0.001) in individuals who carried homozygous or heterozygous variant type genotypes of both genes in a reference with carriers of both wild-type genotypes (wt/wt - wt/wt). The odds ratios were 2.99 (95% CI 1.67-5.36), 2.68 (95% CI 1.08-6.62), and 2.80 (95% CI 1.18-6.69) for those who carried (wt/wt - wt/vt + vt/vt), (wt/vt + vt/vt - wt/wt), and (wt/vt + vt/vt - wt/vt + vt/vt), respectively. The study suggests a limited correlation is present between carrying OGG1 Ser326Cys polymorphism and the risk of developing LC in Arab populations.
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Affiliation(s)
- Bassam K Kudhair
- Department of Laboratory Investigations, Faculty of Science, University of Kufa, 54001, Najaf, Iraq.
| | - Noralhuda N Alabid
- Department of Urban Planning, Faculty of Physical Planning, University of Kufa, 54001, Najaf, Iraq
| | - Karrar S Zayed
- Department of Laboratory Investigations, Faculty of Science, University of Kufa, 54001, Najaf, Iraq
| | - Inam J Lafta
- Department of Microbiology, College of Veterinary Medicine, University of Baghdad, Baghdad, 10071, Iraq
| | - Asghar Taheri-Kafrani
- Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, 81746-73441, Isfahan, Iran
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Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients. Int J Mol Sci 2020; 21:ijms21072473. [PMID: 32252452 PMCID: PMC7177219 DOI: 10.3390/ijms21072473] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 03/30/2020] [Accepted: 03/31/2020] [Indexed: 12/12/2022] Open
Abstract
Oxidative stress with subsequent premutagenic oxidative DNA damage has been implicated in colorectal carcinogenesis. The repair of oxidative DNA damage is initiated by lesion-specific DNA glycosylases (hOGG1, NTH1, MUTYH). The direct evidence of the role of oxidative DNA damage and its repair is proven by hereditary syndromes (MUTYH-associated polyposis, NTHL1-associated tumor syndrome), where germline mutations cause loss-of-function in glycosylases of base excision repair, thus enabling the accumulation of oxidative DNA damage and leading to the adenoma-colorectal cancer transition. Unrepaired oxidative DNA damage often results in G:C>T:A mutations in tumor suppressor genes and proto-oncogenes and widespread occurrence of chromosomal copy-neutral loss of heterozygosity. However, the situation is more complicated in complex and heterogeneous disease, such as sporadic colorectal cancer. Here we summarized our current knowledge of the role of oxidative DNA damage and its repair on the onset, prognosis and treatment of sporadic colorectal cancer. Molecular and histological tumor heterogeneity was considered. Our study has also suggested an additional important source of oxidative DNA damage due to intestinal dysbiosis. The roles of base excision repair glycosylases (hOGG1, MUTYH) in tumor and adjacent mucosa tissues of colorectal cancer patients, particularly in the interplay with other factors (especially microenvironment), deserve further attention. Base excision repair characteristics determined in colorectal cancer tissues reflect, rather, a disease prognosis. Finally, we discuss the role of DNA repair in the treatment of colon cancer, since acquired or inherited defects in DNA repair pathways can be effectively used in therapy.
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11
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Singh A, Singh N, Behera D, Sharma S. Genetic Investigation of Polymorphic OGG1 and MUTYH Genes Towards Increased Susceptibility in Lung Adenocarcinoma and its Impact on Overall Survival of Lung Cancer Patients Treated with Platinum Based Chemotherapy. Pathol Oncol Res 2019; 25:1327-1340. [PMID: 29209987 DOI: 10.1007/s12253-017-0372-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2017] [Accepted: 11/29/2017] [Indexed: 12/12/2022]
Abstract
Genes OGG1 and MUTYH are the two primary genes in Base excision repair pathway. OGG1 hydrolyzes the sugar phosphate backbone and remove the damaged base creating abasic site. MUTYH complements OGG1 as it particularly remove adenine mispaired with 8-oxo-G. Both OGG1 and MUTYH act as a check for the mis-incorporation of bases may be due to damages incurred on DNA. DNA isolation for 326 lung cancer cases and 330 controls was followed by genotyping making use of PCR-RFLP. Logistic regression was done to analyze the risk towards lung cancer. Patients were followed through telephonic conversation. Kaplan meier and Cox-regression were used for survival analysis. OGG1 presented a high risk towards lung cancer (CG: OR = 2.44, p = 0.0003; CG + GG: OR = 1.88, p = 0.0093). On the same lines adenocarcinoma for OGG1 were potent risk factors towards lung cancer (CG: OR = 4.72, p = 0.0002; CG + GG: OR = 3.63, p = 0.0018). Single allelic carriers for MUTYH gene imposed a high risk towards overall lung susceptibility and for all the three histology. Stratified analysis for chemotherapeutic drugs revealed administration of Cisplatin/Carboplatin + Pemtrexed for OGG1Ser 326 Cys showed a better survival (MST CG vs. CC: 9.1 vs. 0.56, p = <0.0001; HR =0.051, p = 0.0025). Whereas, MUTYH Gln324His showed a smaller survival for mutant genotype (CC) (MST CC vs. GG: 4.0 vs. 9.4, p = 0.05; HR = 1.75, p = 0.26). Single allelic carriers for both OGG1 and MUTYH were risk factors towards lung cancer. The risk was amplified on combining both OGG1 and MUTYH.
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MESH Headings
- Adenocarcinoma of Lung/drug therapy
- Adenocarcinoma of Lung/genetics
- Adenocarcinoma of Lung/mortality
- Adenocarcinoma of Lung/pathology
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Biomarkers, Tumor/genetics
- Carcinoma, Non-Small-Cell Lung/drug therapy
- Carcinoma, Non-Small-Cell Lung/genetics
- Carcinoma, Non-Small-Cell Lung/mortality
- Carcinoma, Non-Small-Cell Lung/pathology
- Carcinoma, Squamous Cell/drug therapy
- Carcinoma, Squamous Cell/genetics
- Carcinoma, Squamous Cell/mortality
- Carcinoma, Squamous Cell/pathology
- Case-Control Studies
- DNA Glycosylases/genetics
- Female
- Follow-Up Studies
- Gene Expression Regulation, Neoplastic
- Genetic Predisposition to Disease
- Genotype
- Humans
- Lung Neoplasms/drug therapy
- Lung Neoplasms/genetics
- Lung Neoplasms/mortality
- Lung Neoplasms/pathology
- Male
- Middle Aged
- Organoplatinum Compounds/therapeutic use
- Polymorphism, Single Nucleotide
- Prognosis
- Risk Factors
- Small Cell Lung Carcinoma/drug therapy
- Small Cell Lung Carcinoma/genetics
- Small Cell Lung Carcinoma/mortality
- Small Cell Lung Carcinoma/pathology
- Survival Rate
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Affiliation(s)
- Amrita Singh
- Department of Biotechnology, Thapar University, Patiala, Punjab, 147002, India
| | - Navneet Singh
- Department of Pulmonary Medicine, Post Graduate Institute of Medical Education and Research (PGIMER), Sector 14, Chandigarh, India
| | - Digambar Behera
- Department of Pulmonary Medicine, Post Graduate Institute of Medical Education and Research (PGIMER), Sector 14, Chandigarh, India
| | - Siddharth Sharma
- Department of Biotechnology, Thapar University, Patiala, Punjab, 147002, India.
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12
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Liu J, Zheng B, Li Y, Yuan Y, Xing C. Genetic Polymorphisms of DNA Repair Pathways in Sporadic Colorectal Carcinogenesis. J Cancer 2019; 10:1417-1433. [PMID: 31031852 PMCID: PMC6485219 DOI: 10.7150/jca.28406] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Accepted: 01/12/2019] [Indexed: 12/20/2022] Open
Abstract
DNA repair systems play a critical role in maintaining the integrity and stability of the genome, which mainly include base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR) and double-strand break repair (DSBR). The polymorphisms in different DNA repair genes that are mainly represented by single-nucleotide polymorphisms (SNPs) can potentially modulate the individual DNA repair capacity and therefore exert an impact on individual genetic susceptibility to cancer. Sporadic colorectal cancer arises from the colorectum without known contribution from germline causes or significant family history of cancer or inflammatory bowel disease. In recent years, emerging studies have investigated the association between polymorphisms of DNA repair system genes and sporadic CRC. Here, we review recent insights into the polymorphisms of DNA repair pathway genes, not only individual gene polymorphism but also gene-gene and gene-environment interactions, in sporadic colorectal carcinogenesis.
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Affiliation(s)
- Jingwei Liu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China
| | - Bowen Zheng
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China
| | - Ying Li
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China
| | - Chengzhong Xing
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China
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13
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Huang HI, Chen CH, Wang SH, Wang LH, Lin YC. Effects of APE1 Asp148Glu polymorphisms on OPMD malignant transformation, and on susceptibility to and overall survival of oral cancer in Taiwan. Head Neck 2019; 41:1557-1564. [PMID: 30652382 DOI: 10.1002/hed.25576] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 09/13/2018] [Accepted: 12/05/2018] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND The associations between malignant transformation of oral potentially malignant disorders (OPMDs), oral cancer development and prognosis, and apurinic/apyrimidinic endonuclease 1 (APE1) functional polymorphisms are unclear. METHODS Patients with OPMDs, patients with oral cancer, and healthy controls from the community were recruited to determine the effects of APE1 polymorphisms on malignant transformation, overall survival, and genetic susceptibility, respectively. RESULTS The APE1 Asp148Glu polymorphisms significantly correlated with a high hazard ratio for OPMD malignant transformation (adjusted hazard ratio [AHR] = 2.29; 95% confidence interval [CI] = 1.44-3.74) and low overall survival in oral cancer patients (AHR = 1.71, 95% CI = 1.11-2.56) according to follow-up and survival analysis. However, APE1 polymorphisms did not significantly correlate with development of oral cancer in the case-control study and logistic regression analysis. CONCLUSIONS These results indicate that APE1 Asp148Glu polymorphisms may have indirect roles in increasing the OPMD malignant transformation rate and in decreasing overall survival in oral cancer patients.
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Affiliation(s)
- Hsin-I Huang
- School of Dentistry, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Ho Chen
- Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Sheng-Hung Wang
- School of Dentistry, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Li-Hsuan Wang
- Division of Molecular Diagnosis, Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ying-Chu Lin
- School of Dentistry, Kaohsiung Medical University, Kaohsiung, Taiwan
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14
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Kamiza AB, Hsieh L, Tang R, Chien H, Lai C, Chiu L, Lo T, Hung K, You J, Wang W, Hsiung CA, Yeh C. Polymorphisms of DNA repair genes are associated with colorectal cancer in patients with Lynch syndrome. Mol Genet Genomic Med 2018; 6:533-540. [PMID: 29664240 PMCID: PMC6081223 DOI: 10.1002/mgg3.402] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2017] [Revised: 02/04/2018] [Accepted: 03/12/2018] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND DNA repair genes are crucial for maintaining genomic stability by preventing mutagenesis and carcinogenesis. The present retrospective cohort study aimed at investigating whether MLH1, APEX1, MUTYH, OGG1, NUDT1, XRCC5, XPA, and ERCC2 single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in Chinese population with Lynch syndrome. METHODS From Amsterdam criteria family registry, we identified 270 patients with Lynch syndrome. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between DNA repair SNPs and CRC were calculated using a weighted Cox proportional hazard regression model. RESULTS Heterozygous variants of rs1799832 in NUDT1 (HR = 2.97, 95% CI = 1.51-5.83) and rs13181 in ERCC2 (HR = 2.69, 95% CI = 1.10-6.55) were significantly associated with an increased risk of CRC compared with wild-type homozygous CC and TT genotypes, respectively. However, the variant CG+GG genotype of MUTYH rs3219489 was associated with a decreased risk of CRC (HR = 0.49, 95% CI = 0.26-0.91) compared with the homozygous CC wild-type counterparts. CONCLUSION Our findings revealed that polymorphisms of DNA repair genes that include NUDT1, ERCC2, and MUTYH are associated with CRC in patients with Lynch syndrome in Chinese population. Further studies with large sample size are needed to confirm our findings.
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Affiliation(s)
- Abram B. Kamiza
- School of Public HealthCollege of Public HealthTaipei Medical UniversityTaipeiTaiwan
| | - Ling‐Ling Hsieh
- Department of Public HealthCollege of MedicineChang Gung UniversityTaoyuanTaiwan
| | - Reiping Tang
- Colorectal SectionDepartment of SurgeryChang Gung Memorial HospitalTaoyuanTaiwan
- School of MedicineChang Gung UniversityTaoyuanTaiwan
| | - Huei‐Tzu Chien
- Department of Public HealthCollege of MedicineChang Gung UniversityTaoyuanTaiwan
- Department of Nutrition and Health SciencesChang Gung University of Science and TechnologyTaoyuanTaiwan
| | - Chih‐Hsiung Lai
- Department of Public HealthCollege of MedicineChang Gung UniversityTaoyuanTaiwan
| | - Li‐Ling Chiu
- Department of Public HealthCollege of MedicineChang Gung UniversityTaoyuanTaiwan
- Department of Nutrition and Health SciencesChang Gung University of Science and TechnologyTaoyuanTaiwan
| | - Tsai‐Ping Lo
- Institute of Population Health SciencesNational Health Research InstitutesMiaoliTaiwan
| | - Kuan‐Yi Hung
- Institute of Population Health SciencesNational Health Research InstitutesMiaoliTaiwan
| | - Jeng‐Fu You
- Colorectal SectionDepartment of SurgeryChang Gung Memorial HospitalTaoyuanTaiwan
- School of MedicineChang Gung UniversityTaoyuanTaiwan
| | - Wen‐Chang Wang
- Ph.D. Program for Translational MedicineCollege of Medical Science and TechnologyTaipei Medical UniversityTaipeiTaiwan
| | - Chao A. Hsiung
- Institute of Population Health SciencesNational Health Research InstitutesMiaoliTaiwan
| | - Chih‐Ching Yeh
- School of Public HealthCollege of Public HealthTaipei Medical UniversityTaipeiTaiwan
- Department of Public HealthChina Medical UniversityTaichungTaiwan
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