A pooled analysis of host factors that affect nucleotide excision repair in humans.

Jana Slyskova, Mirta Milic, Irene Orlow, Sergey Shaposhnikov, Gunnar Brunborg, Sabine A S Langie, Roger Godschalk, Pavel Vodicka, Andrew Collins, Maria Dusinska, Amaya Azqueta, Stefano Bonassi, Frederik-Jan van Schooten, Congying Zheng

Journal: Mutagenesis 2025;40(2):137-144

PMID: 39670868

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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 analyse 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 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 = .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 = .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 = .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.

Address: Department of Pharmacology and Toxicology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200 Maastricht, The Netherlands.; Norgenotech AS, Ullernchassern, 64/66, 0379 Oslo, Norway.; Oslo Cancer Cluster, Ullernchausseen, 64/66, 0379 Oslo, Norway.; Norgenotech AS, Ullernchassern, 64/66, 0379 Oslo, Norway.; Oslo Cancer Cluster, Ullernchausseen, 64/66, 0379 Oslo, Norway.; Norgenotech AS, Ullernchassern, 64/66, 0379 Oslo, Norway.; Department of Pharmaceutical Sciences, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.; Department of Pharmacology and Toxicology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200 Maastricht, The Netherlands.; Department of Environmental Chemistry and Health, Health Effects Laboratory, The Climate and Environmental Research Institute NILU, 2027 Kjeller, Norway.; Department of the Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 00 Prague, Czech Republic.; Department of the Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 00 Prague, Czech Republic.; Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/77, 32300 Pilsen, Czech Republic.; Unit of Clinical and Molecular Epidemiology, IRCCS San Raffaele Roma, 00163 Rome, Italy.; Department of Human Sciences and Quality of Life Promotion, San Raffaele University, Unit of Clinical and Molecular Epidemiology, IRCCS San Raffaele Roma, Via di Val Cannuta, 247, 00166, Rome, Italy.; Division of Toxicology, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000, Zagreb, Croatia.; Memorial Sloan-Kettering Cancer, Department of Epidemiology and Biostatistics, New York, NY 10065, USA.

DOI: 10.1093/mutage/geae028

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MeSH Terms: Humans, DNA Repair, Female, Male, Adult, Aged, Middle Aged, Body Mass Index, Leukocytes, Mononuclear, DNA Damage, Sex Factors, Smoking, Age Factors, Comet Assay, Excision Repair