Environmental and Molecular Mutagenesis最新文献

{"title":"Oxidative DNA Damage Exacerbates the Mutagenic Potential of Alternative DNA Structures via Altered DNA Repair Processing.","authors":"Alex W Klattenhoff, Maha Zewail-Foote, Arti Madan, Anna Chiu, Karen M Vasquez","doi":"10.1002/em.70059","DOIUrl":"10.1002/em.70059","url":null,"abstract":"<p><p>Alternative DNA structure-forming (i.e., non-B) sequences such as H-DNA-forming sequences are enriched at chromosomal translocation hotspots in human cancer genomes, underscoring their role in genomic instability. H-DNA is particularly susceptible to DNA damage by reactive oxygen species (ROS), a common byproduct from both endogenous metabolism and environmental contaminants, thereby exacerbating its mutagenic potential. Oxidative lesions within B-DNA are efficiently processed by base excision repair (BER), whereas H-DNA is processed in a mutagenic fashion by nucleotide excision repair (NER). Thus, we speculate that the repair of oxidative lesions within H-DNA will promote aberrant BER and NER processing, ultimately enhancing mutagenesis. Here, we examine the processing of oxidative damage within H-DNA by measuring the changes in mutation frequencies and spectra, as well as the association with key NER and BER proteins in human cells in the presence or absence of specific DNA repair proteins. Our results demonstrate that oxidatively damaged H-DNA serves as a substrate for both BER and NER and reveals an interplay between BER and NER proteins, which influences mutation outcomes. This novel framework establishes a link between oxidative stress, DNA repair, and H-DNA-associated mutagenesis, providing insight into how environmentally relevant DNA damage can drive sequence-specific genomic instability at cancer-associated hotspots.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 4","pages":"e70059"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13145318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benchmark Response Values for Error-Corrected Sequencing Mutagenicity Assessment Technologies.","authors":"Saron Mulugeta, Francesco Marchetti, Guangchao Chen, Connie Chen, Raechel Puglisi, Paul A White","doi":"10.1002/em.70051","DOIUrl":"https://doi.org/10.1002/em.70051","url":null,"abstract":"<p><p>The Benchmark Dose (BMD) approach is commonly used to determine Point-of-Departure (PoD) values for risk assessment and regulatory decision-making; however, choosing a suitable Benchmark Response (BMR) for continuous endpoints is a challenge. Earlier work established a BMR of 50% for selected in vivo mutagenicity endpoints (i.e., Transgenic Rodent and Pig-a). Error-corrected sequencing (ECS) technologies, such as Duplex Sequencing (DupSeq), Hawk-Seq, PECC-Seq, and PacBio HiFi, have emerged as powerful tools for mutagenicity assessment. This study applied and compared two approaches for defining BMR values for ECS technologies: the Effect Size (ES) theory of Slob (2017), and the one standard deviation approach of Zeller et al. (2017). A dose-response database of ECS studies was compiled to determine technology-specific within-group variance values (var) for BMR determination. Experimental factor influences on var, including species, rodent strain, administration route, application time, tissue type, tissue sampling time, and DNA fragmentation method, were examined; no significant influences were detected. The absence of covariate effects justified using typical, technology-specific var values for BMR determinations. Using these values, technology-specific BMRs were calculated as 27.7% for DupSeq, 16.6% for Hawk-Seq, and 23.3% for PECC-Seq. BMRs derived from negative control values were 22.6 to 28.8% for DupSeq, 5.6 to 13.8% for Hawk-Seq, 28.7 to 31.5% for PECC-Seq, and 9.5 to 22.8% for PacBio HiFi. These findings support adoption of a 30% BMR for in vivo ECS mutagenicity assessment technologies, providing a robust and consistent foundation for future dose-response modeling and human health risk assessment.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 4","pages":"e70051"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13112513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjusting the Preincubation Conditions to Enhance the Ames Test for Detecting the Mutagenicity of N-Nitrosamines.","authors":"Michelle E Bishop, Audrey M Sims, Sharon K Guerrero, Kamela Mitchell, Nan Mei, Hannah Xu, Naomi L Kruhlak, Sruthi T King, Robert T Dorsam, Aisar H Atrakchi, Timothy J McGovern, Robert H Heflich","doi":"10.1002/em.70041","DOIUrl":"https://doi.org/10.1002/em.70041","url":null,"abstract":"<p><p>Conducting S9-mediated preincubations at slightly acid pHs (e.g., pH 5.0 to pH 6.5) has been reported to enhance the mutagenicity of small-molecule nitrosamines in the Ames test. In this study, we have evaluated the effect of adjusting the preincubation mix used in the Enhanced Ames Test (EAT) from pH 7.4 to pH 6.0 and supplying the activation mix with preformed reducing equivalents (NADPH and NADH). Abbreviated EAT assays were conducted on five small-molecule N-nitrosamines and 10 nitrosamine drug substance-related impurities (NDSRIs) with tester strains TA1535 and WP2 uvrA (pKM101) and using S9 mixes containing 30% hamster liver S9. Testing on small-molecule nitrosamines found that the pH 6.0 preincubation mix enhanced the mutagenicity of N-nitroso-dimethylamine and N-nitroso-diethylamine but not N-nitroso-diphenylamine, N-nitroso-methyl-4-aminobutyric acid or N-(2,2-diethoxyethyl)-2,2-diethoxy-N-nitrosoethanamine. Of the 10 NDSRIs that were tested, N-nitroso-phenylephrine was consistently positive with the pH 6.0 preincubation mix, while it was generally negative with pH 7.4 preincubation mixes. The mutagenicity of the nine other NDSRIs that were tested was not changed by the slightly acid preincubation mix. The results indicate that performing preincubation reactions under slightly acid conditions increases the mutagenicity of some small-molecule nitrosamines, and in one case, produced a positive mutagenic response with an NDSRI that was otherwise negative in the EAT.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 3","pages":"e70041"},"PeriodicalIF":2.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Survey of DNA Damage in American Alligators (Alligator mississippiensis) in Florida.","authors":"Haiyan Lu, Idoia Meaza, Rachel M Wise, James T F Wise, Sandra S Diven, Tayler J Croom-Pérez, Jennifer H Toyoda, John Pierce Wise","doi":"10.1002/em.70047","DOIUrl":"https://doi.org/10.1002/em.70047","url":null,"abstract":"<p><p>The scientific concept of One Environmental Health is a research strategy focused on the study of toxicants, aiming to incorporate human, wildlife, and ecosystem health to establish a more comprehensive understanding of health. A One Environmental Health approach, studying the responses of American alligators (Alligator mississippiensis) that are considered apex sentinel organisms to environmental toxicants, is crucial. Due to their long-lived lifestyle on land and water, including a wide range of prey items in their diet and their ability to bioaccumulate metals, alligators serve as effective indicators of heavy metal pollution, which poses risks to aquatic ecosystems and human health. In this study, we examined DNA damage in American alligators from three locations in Florida using comet assay. We found alligators in Merritt Island National Wildlife Refuge had significantly higher DNA damage levels compared to those in Lake Apopka and Lake Woodruff. This trend was consistent across both sexes, with no observed sex differences. Similarly, DNA damage levels were significantly higher in both adult and juvenile alligators from Merritt Island compared to the other locations. Notably, juvenile alligators exhibited higher DNA damage than adults, with animals from Merritt Island exhibiting particularly elevated levels.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 3","pages":"e70047"},"PeriodicalIF":2.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin C Regulates Redox Homeostasis and Mitigates Potassium Bromate-Induced Oxidative Injury to Rat Intestine.","authors":"Saima Nazir, Mir Kaisar Ahmad, Zubair-Ul-Nazir","doi":"10.1002/em.70045","DOIUrl":"https://doi.org/10.1002/em.70045","url":null,"abstract":"<p><p>Potassium bromate (KBrO₃), a probable human carcinogen, is generated as a disinfection by-product during ozonation of water and is also used as a flour maturing agent. It has been shown to induce oxidative damage and subsequent tissue-toxicity in individuals who get exposed to it. Previously, we have reported that KBrO₃ induces oxidative stress and subsequent intestinal toxicity, as is evident from DNA damage and the histological studies. In the present study, the protective efficacy of dietary antioxidant vitamin C on KBrO₃-induced intestinal toxicity has been explored. Administration of KBrO₃ led to a decrease (almost 1.5 fold) in the brush border membrane enzymatic activities. The oxidative reductive homeostasis of the intestine was greatly affected, as reflected by the severe alterations in the antioxidant enzymatic system, besides altering the carbohydrate metabolism too. There was also an increase in DNA damage (+1.5 fold) and DNA-protein cross-linking (+2 fold). However, pretreatment with vitamin C resulted in significant attenuation/modulation in all these parameters. The biochemical studies were supported by the histological studies showing extensive intestinal damage in KBrO₃-treated animals and greatly reduced tissue injury in the vitamin C + KBrO₃ group. These results show that vitamin C mitigates bromate-induced intestinal toxic insult and oxidative damage by improving antioxidant defense, tissue integrity, and energy metabolism and thus can be used as a therapeutic/protective agent against bromate and its related compounds.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 3","pages":"e70045"},"PeriodicalIF":2.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alizarin Dye: Toxicity, Genotoxicity, and Histopathological Alterations in Model Organisms.","authors":"Amanda Rocha Rodrigues, Gabriela Cristina Fonseca Almeida, Natália Oliveira de Farias, Anjaina Fernandes de Albuquerque, Adria Caloto de Oliveira, Jessica Camila Miranda Cardoso, Gabriely Fernanda Groto Militão, Inês Moutinho Cabral, Catarina A Faustino, João D Vitorino, Marina Tenório Botelho, Pedro M Costa, Gisela de Aragão Umbuzeiro","doi":"10.1002/em.70046","DOIUrl":"https://doi.org/10.1002/em.70046","url":null,"abstract":"<p><p>Alizarin is an anthraquinone red dye from natural or synthetic sources, widely used in textiles. Effluents of this activity can contain residual dyes, which may contaminate the aquatic environment. Studies report alizarin's aquatic toxicity, mutagenic, and carcinogenic effects. This study aimed to complement the aquatic toxicity evaluation and confirm its ability to cause genotoxicity in alternative models. Acute toxicity was performed with crustaceans, mussels, and fish embryos, while chronic toxicity was assessed in algae. Light effects on toxicity were evaluated using Daphnia similis. Histopathological effects on the gonads of Mytilus galloprovincialis and somatic mutations and sperm genotoxicity in Parhyale hawaiensis were investigated. Mutagenicity was confirmed using a miniaturized Ames test. The effect concentration 50% (EC₅₀) for D. similis was 90.3, 105, and 68.6 μg L^-1 for photoperiod (16 h light:8 h dark), light and dark, respectively. For Danio rerio embryos, the lethal concentration 50% (LC₅₀) was 45.8 μg L^-1, and an EC₁₀ of 20.8 μg L^-1 was calculated for sublethal effects. In vivo exposures caused alterations in the digestive gland and gonads of M. galloprovincialis, even in a short-term exposure, and increased the frequency of micronuclei and DNA damage in hemocytes and spermatozoids, respectively, of P. hawaiensis. It was mutagenic in the miniaturized Ames test using strain TA1537 (10% and 30% S9). Alizarin can be classified as a Category 1 acute aquatic toxicity according to the globally harmonized system (GHS). Due to adverse histopathological and DNA effects on reproductive systems in model organisms, it is considered a potential germ cell mutagen.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 3","pages":"e70046"},"PeriodicalIF":2.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Assessment of DNA Damage in PBMCs From Hospitalized COVID-19 Patients via Alkaline Comet Assay.","authors":"Lenin Rueda-Torres, Dulce E Alarcón-Yaquetto, Beatriz Ayala-Quintanilla, Germán Málaga, Jaime Rosales-Rimache","doi":"10.1002/em.70055","DOIUrl":"https://doi.org/10.1002/em.70055","url":null,"abstract":"<p><p>Growing evidence suggests an association between SARS-CoV-2 infection and oxidative stress-related genomic damage, primarily from cross-sectional studies. However, longitudinal evaluations remain limited. Here, we assessed DNA damage in peripheral blood mononuclear cells (PBMCs) from hospitalized COVID-19 patients during the first days of hospitalization, using the alkaline comet assay. A longitudinal descriptive study was conducted at a modular COVID-19 hospital in Lima, Peru, throughout October 2020. Blood samples were collected at admission (day 0), day 3, and day 6. DNA damage was assessed by measuring tail length, tail moment, and tail intensity, which were modeled using mixed-effects linear models. Concurrent hematological parameters and acute-phase proteins were also analyzed to characterize their time-course patterns in conjunction with DNA damage. Results from the adjusted mixed-effects model showed a significant temporal increase in DNA damage parameters, particularly tail intensity (β = 0.25 per day, p = 0.003), relative to baseline measurements, with a peak observed on day 3 of hospitalization. These changes aligned with variations in platelet counts and transferrin levels, while lymphocyte and monocyte counts, along with C-reactive protein, showed an inverse trend, reflecting the dynamic interplay of the inflammatory response and DNA damage. No significant differences in comet assay parameters were observed between survivors and non-survivors, likely due to the limited and unbalanced sample. The findings indicate the presence of a measurable DNA damage burden in PBMCs of hospitalized COVID-19 patients, highlighting the need to further studies to clarify the mechanisms underlying DNA damage and its potential long-term biological implications.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 3","pages":"e70055"},"PeriodicalIF":2.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymorphisms in CLAUDIN1 and SPINK5 Influence Skin Absorption of Pyrene, Pyrimethanil, and Oxybenzone in Human Volunteers.","authors":"Emmy Keysendal, Gunnar Johanson, Lina Hagvall, Nanna Fyhrqvist, Christian Lindh, Karin Broberg, Emelie Rietz Liljedahl","doi":"10.1002/em.70050","DOIUrl":"https://doi.org/10.1002/em.70050","url":null,"abstract":"<p><p>Absorption of chemicals through the skin affects occupational and environmental exposure to diverse compounds. We previously showed that loss-of-function (null) mutations and low-copy number variants (CNV) of Filaggrin (FLG), which encodes a key skin barrier protein, increased dermal chemical absorption; however, the FLG genotype did not explain all the observed variation. Here, we explore the effects of variation in genes encoding skin proteins that could affect chemical uptake. In a dermal exposure test, 23 null-FLG and 31 wild-type carriers were exposed to three common organic compounds: the polycyclic aromatic hydrocarbon pyrene, the fungicide pyrimethanil, and the ultraviolet-light absorber oxybenzone. Liquid chromatography-mass spectrometry was used to measure the concentrations of these chemicals or their metabolites in the subjects' urine collected over a 40-h period following exposure. We genotyped the participants for 14 polymorphisms in seven skin function-related genes (Filaggrin 2 [FLG2], including a new method for assessing FLG2 CNV, claudin 1 [CLDN1], serine peptidase inhibitor kazal type 5 [SPINK5], S100 calcium binding protein A7 [S100A7], transmembrane protein 79 [TMEM79], laminin subunit alpha 3 [LAMA3], and involucrin [IVL]) and performed a population toxicokinetic analysis. While controlling for FLG genotype, the CLDN1 rs893051 minor allele was associated with increased absorption, faster absorption rate, and longer lag time, while the SPINK5 rs2303067 minor allele was associated with shorter lag time. However, the differences in total systemic absorption were minor compared with FLG variants. Thus, FLG remains the predominant genetic determinant of chemical uptake through the skin.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"67 3","pages":"e70050"},"PeriodicalIF":2.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The In Vitro Transgenic Rodent Assay in Primary MutaMouse Hepatocytes Compared to the Mammalian Cell Gene Mutation Assay Using the HPRT Gene.","authors":"Alina Göpfert, Kylee Kendra Marie Ronnenberg, Claudia Ruelker, Silke Spang, Naveed Honarvar, Robert Landsiedel","doi":"10.1002/em.70040","DOIUrl":"10.1002/em.70040","url":null,"abstract":"<p><p>Gene mutations can be detected in mammalian cells in vitro using indicator genes such as the hypoxanthine-guanine-phosphoribosyltransferase (HPRT) gene. These assays have been adopted as OECD test guidelines (TG, e.g., OECD TG no. 476) and are used for regulatory purposes. The in vitro transgenic rodent assay (TGRA) in primary MutaMouse hepatocytes is a novel approach for the detection and quantification of gene mutations. Its methodology follows the same principles as the in vivo TGRA, an in vivo gene mutation assay with regulatory adoption (OECD TG no. 488). Although the potential of the in vitro TGRA to identify mutagens has been reported, its performance compared to an established in vitro gene mutation assay has not been reported. This study compared the in vitro TGRA with the HPRT assay using 10 known in vivo mutagens. The in vitro TGRA correctly identified all 10 mutagens, whereas the HPRT assay identified only nine. Benchmark concentration (BMC) modeling for the nine substances detected by both assays revealed overlapping confidence intervals for six compounds, indicating comparable sensitivity. For three mutagens, the HPRT assay yielded lower BMC intervals. Additionally, eight substances known to be non-mutagenic in vivo tested negative in the in vitro TGRA. While increased cytotoxicity did not induce increased mutant frequencies, it reduced DNA yield, thereby impairing mutagenicity assessment. The results of this study contribute to the understanding of the sensitivity and robustness of the in vitro TGRA and provide essential information for the validation of the assay.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":" ","pages":"e70040"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145387923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-Analysis of CYP1A1 MspI and Ile462Val Polymorphisms in Cancer Susceptibility Among Different Ethnic Populations.","authors":"Amjad Yousuf, Najeeb Ullah Khan, Ahsanullah Unar","doi":"10.1002/em.70042","DOIUrl":"10.1002/em.70042","url":null,"abstract":"<p><p>The Cytochrome P450 1A1 (CYP1A1) gene plays a crucial role in the production of enzymes involved in the metabolic activation and detoxification of harmful carcinogens, which are essential for genetic susceptibility to cancer. Due to the inconsistent findings obtained from population-based studies, it is crucial to systematically investigate the association between CYP1A1 polymorphisms and diverse ethnic groups. To assess the link between CYP1A1 polymorphisms and cancer risk across different ethnic populations. The studies published in the last decade were searched through PubMed, Cochrane Library, and Embase, based on PRISMA guidelines and eligibility criteria. Meta-analysis includes subgroup analysis based on ethnicity with odds ratio (OR) and 95% confidence intervals through R Studio. Genotypic and allelic data were analyzed under genetic models (allelic, dominant, and recessive) using a random-effects model. The quality of the included case-control studies was assessed using the Newcastle-Ottawa scale. Twenty case-control studies containing various ethnic populations, of which eleven contain the MspI polymorphism, and the other nine contain the Ile462Val polymorphism of the CYP1A1, while none explained both SNPs. The research studies involved 3976 cases and 4891 controls in this meta-analysis. For MspI polymorphisms, the overall pooled analysis revealed a significant association with cancer risk in the Brazilian ethnic group (2.46 [95% CI: 0.00; 305699178.1]) with moderate heterogeneity observed within the genetic models of CYP1A1 polymorphisms. For Ile462Val polymorphisms, the overall pooled effect size was significant among the Asian group (2.11 [95% CI: 1.45; 3.06]). Meanwhile, the subgroup analysis provides some evidence of cancer risk association with polymorphisms among different ethnicities. The results of this meta-analysis indicate that the understanding of CYP1A1 polymorphisms is necessary to determine the etiology of cancer. The significant association among CYP1A1 polymorphisms and cancer can further be studied by selecting studies focused on a particular cancer type and containing a large sample size within a specific ethnic population.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":" ","pages":"e70042"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145713358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}