Congying Zheng, Sergey Shaposhnikov, Andrew Collins, Gunnar Brunborg, Amaya Azqueta, Sabine A S Langie, Maria Dusinka, Jana Slyskova, Pavel Vodicka, Frederik-Jan van Schooten, Stefano Bonassi, Mirta Milic, Irene Orlow, Roger Godschalk
{"title":"A pooled analysis of host factors that affect nucleotide excision repair in humans.","authors":"Congying Zheng, Sergey Shaposhnikov, Andrew Collins, Gunnar Brunborg, Amaya Azqueta, Sabine A S Langie, Maria Dusinka, Jana Slyskova, Pavel Vodicka, Frederik-Jan van Schooten, Stefano Bonassi, Mirta Milic, Irene Orlow, Roger Godschalk","doi":"10.1093/mutage/geae028","DOIUrl":null,"url":null,"abstract":"<p><p>Nucleotide excision repair (NER) is crucial for repairing bulky lesions and crosslinks in DNA caused by exogenous and endogenous genotoxins. The number of studies that have considered DNA repair as a biomarker is limited, and therefore one of the primary objectives of the European COST Action hCOMET (CA15132) was to assemble and analyze a pooled database of studies with data on NER activity. The database comprised 738 individuals, gathered from 5 laboratories that ran population studies using the comet-based in vitro DNA repair assay. NER activity data in peripheral blood mononuclear cells (PBMCs) were normalized and correlated with various host-related factors, including sex, age, body mass index (BMI), and smoking habits. This multifaceted analysis uncovered significantly higher NER activity in female participants compared to males (1.08 ± 0.74 vs. 0.92 ± 0.71; P = 0.002). Higher NER activity was seen in older subjects (> 30 years), and the effect of age was most pronounced in the oldest females, particularly those over 70 years (P = 0.001). Females with a normal BMI (< 25 kg/m2) exhibited the highest levels of NER, whereas the lowest NER was observed in overweight males (BMI ≥ 25 kg/m2). No independent effect of smoking was found. After stratification by sex and BMI, higher NER was observed in smoking males (P = 0.017). The biological implication of higher or lower repair capacity remains unclear; the inclusion of DNA repair as a biomarker in molecular epidemiological trials should elucidate the link between health and disease status.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":""},"PeriodicalIF":2.5000,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mutagenesis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/mutage/geae028","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Nucleotide excision repair (NER) is crucial for repairing bulky lesions and crosslinks in DNA caused by exogenous and endogenous genotoxins. The number of studies that have considered DNA repair as a biomarker is limited, and therefore one of the primary objectives of the European COST Action hCOMET (CA15132) was to assemble and analyze a pooled database of studies with data on NER activity. The database comprised 738 individuals, gathered from 5 laboratories that ran population studies using the comet-based in vitro DNA repair assay. NER activity data in peripheral blood mononuclear cells (PBMCs) were normalized and correlated with various host-related factors, including sex, age, body mass index (BMI), and smoking habits. This multifaceted analysis uncovered significantly higher NER activity in female participants compared to males (1.08 ± 0.74 vs. 0.92 ± 0.71; P = 0.002). Higher NER activity was seen in older subjects (> 30 years), and the effect of age was most pronounced in the oldest females, particularly those over 70 years (P = 0.001). Females with a normal BMI (< 25 kg/m2) exhibited the highest levels of NER, whereas the lowest NER was observed in overweight males (BMI ≥ 25 kg/m2). No independent effect of smoking was found. After stratification by sex and BMI, higher NER was observed in smoking males (P = 0.017). The biological implication of higher or lower repair capacity remains unclear; the inclusion of DNA repair as a biomarker in molecular epidemiological trials should elucidate the link between health and disease status.
期刊介绍:
Mutagenesis is an international multi-disciplinary journal designed to bring together research aimed at the identification, characterization and elucidation of the mechanisms of action of physical, chemical and biological agents capable of producing genetic change in living organisms and the study of the consequences of such changes.