Associations between DNMT1 Gene Polymorphisms and Cancer Susceptibility: A Systematic Review and Meta-analysis
Objective: For years, it has been acknowledged that cancer cells contribute to aberrant DNA methylation, an epigenetic alteration. DNA methyltransferase 1 (DNMT1) is a large multidomain protein critical DNMT in cells. Due to its significant function in epigenetic control, DNMT1 is a viable candidate...
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Royan Institute (ACECR), Tehran
2024-12-01
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| Series: | Cell Journal |
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| Online Access: | https://www.celljournal.org/article_723111_d41d8cd98f00b204e9800998ecf8427e.pdf |
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| author | Asma Khorshid Shamshiri Maryam Alidoust Fahimeh Afzaljavan |
| author_facet | Asma Khorshid Shamshiri Maryam Alidoust Fahimeh Afzaljavan |
| author_sort | Asma Khorshid Shamshiri |
| collection | DOAJ |
| description | Objective: For years, it has been acknowledged that cancer cells contribute to aberrant DNA methylation, an epigenetic alteration. DNA methyltransferase 1 (DNMT1) is a large multidomain protein critical DNMT in cells. Due to its significant function in epigenetic control, DNMT1 is a viable candidate gene for cancer susceptibility. The relationships between DNMT1 polymorphisms and cancer risk have been investigated; however, the outcomes are inconsistent. This metaanalysis aims to clarify the relationships between DNMT1 polymorphisms and cancer susceptibility.Materials and Methods: PubMed, Web of Science, and Scopus databases were systematically searched using specific search terms to identify potentially eligible papers published before January 2025. Fixed-effects or randomeffects models were employed to calculate odds ratios (OR) and 95% confidence intervals (CI). The I² statistic and Egger’s test were utilised to evaluate inter-study heterogeneity and assess the presence of publication bias among the included studies. All statistical analyses were conducted using MetaGenyo software.Results: A total of 776 articles were retrieved from PubMed, Scopus, and Web of Science databases. After full-text evaluation and applying the literature selection criteria, 23 articles were included as case-control studies that assessed the relationship between 23 polymorphisms in DNMT1 and cancer risk were included. The rs2228612, rs2228611, rs16999593, and rs10420321 single nucleotide polymorphisms (SNPs) were most frequently investigated. The rs2228612 co-dominant model [P=0.037, OR=0.89, 95% CI (0.80-0.99)] and rs2228611 dominant model [P<0.001, OR=1.32, 95% CI (1.14-0.53)] revealed a substantial association with cancer risk. Subgroup analysis showed an association between the rs2228612 co-dominant [P=0.022, OR=0.58, 95% CI (0.74-0.98)] and recessive [P=0.046, OR=1.15, 95% CI (1.00-1.32)] models with gastrointestinal cancer and the rs2228611 co-dominant model with breast cancer [P=0.024, OR=1.15, 95% CI (1.02-1.29)].Conclusion: Although the current study found a role for DNMT1 polymorphisms in cancer risk, further high-quality studies are needed to validate these findings. |
| format | Article |
| id | doaj-art-926b1322a0804e4a87c313c6395ea706 |
| institution | OA Journals |
| issn | 2228-5806 2228-5814 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Royan Institute (ACECR), Tehran |
| record_format | Article |
| series | Cell Journal |
| spelling | doaj-art-926b1322a0804e4a87c313c6395ea7062025-08-20T02:35:36ZengRoyan Institute (ACECR), TehranCell Journal2228-58062228-58142024-12-01261266968110.22074/cellj.2025.2045804.1716723111Associations between DNMT1 Gene Polymorphisms and Cancer Susceptibility: A Systematic Review and Meta-analysisAsma Khorshid Shamshiri0Maryam Alidoust1Fahimeh Afzaljavan2Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Obstetrics and Gynecology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IranObjective: For years, it has been acknowledged that cancer cells contribute to aberrant DNA methylation, an epigenetic alteration. DNA methyltransferase 1 (DNMT1) is a large multidomain protein critical DNMT in cells. Due to its significant function in epigenetic control, DNMT1 is a viable candidate gene for cancer susceptibility. The relationships between DNMT1 polymorphisms and cancer risk have been investigated; however, the outcomes are inconsistent. This metaanalysis aims to clarify the relationships between DNMT1 polymorphisms and cancer susceptibility.Materials and Methods: PubMed, Web of Science, and Scopus databases were systematically searched using specific search terms to identify potentially eligible papers published before January 2025. Fixed-effects or randomeffects models were employed to calculate odds ratios (OR) and 95% confidence intervals (CI). The I² statistic and Egger’s test were utilised to evaluate inter-study heterogeneity and assess the presence of publication bias among the included studies. All statistical analyses were conducted using MetaGenyo software.Results: A total of 776 articles were retrieved from PubMed, Scopus, and Web of Science databases. After full-text evaluation and applying the literature selection criteria, 23 articles were included as case-control studies that assessed the relationship between 23 polymorphisms in DNMT1 and cancer risk were included. The rs2228612, rs2228611, rs16999593, and rs10420321 single nucleotide polymorphisms (SNPs) were most frequently investigated. The rs2228612 co-dominant model [P=0.037, OR=0.89, 95% CI (0.80-0.99)] and rs2228611 dominant model [P<0.001, OR=1.32, 95% CI (1.14-0.53)] revealed a substantial association with cancer risk. Subgroup analysis showed an association between the rs2228612 co-dominant [P=0.022, OR=0.58, 95% CI (0.74-0.98)] and recessive [P=0.046, OR=1.15, 95% CI (1.00-1.32)] models with gastrointestinal cancer and the rs2228611 co-dominant model with breast cancer [P=0.024, OR=1.15, 95% CI (1.02-1.29)].Conclusion: Although the current study found a role for DNMT1 polymorphisms in cancer risk, further high-quality studies are needed to validate these findings.https://www.celljournal.org/article_723111_d41d8cd98f00b204e9800998ecf8427e.pdfdna methyltransferase 1geneticmeta-analysisneoplasmspolymorphism |
| spellingShingle | Asma Khorshid Shamshiri Maryam Alidoust Fahimeh Afzaljavan Associations between DNMT1 Gene Polymorphisms and Cancer Susceptibility: A Systematic Review and Meta-analysis Cell Journal dna methyltransferase 1 genetic meta-analysis neoplasms polymorphism |
| title | Associations between DNMT1 Gene Polymorphisms and Cancer Susceptibility: A Systematic Review and Meta-analysis |
| title_full | Associations between DNMT1 Gene Polymorphisms and Cancer Susceptibility: A Systematic Review and Meta-analysis |
| title_fullStr | Associations between DNMT1 Gene Polymorphisms and Cancer Susceptibility: A Systematic Review and Meta-analysis |
| title_full_unstemmed | Associations between DNMT1 Gene Polymorphisms and Cancer Susceptibility: A Systematic Review and Meta-analysis |
| title_short | Associations between DNMT1 Gene Polymorphisms and Cancer Susceptibility: A Systematic Review and Meta-analysis |
| title_sort | associations between dnmt1 gene polymorphisms and cancer susceptibility a systematic review and meta analysis |
| topic | dna methyltransferase 1 genetic meta-analysis neoplasms polymorphism |
| url | https://www.celljournal.org/article_723111_d41d8cd98f00b204e9800998ecf8427e.pdf |
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