title: Both genetic and dietary factors underlie individual differences in DNA damage levels and DNA repair capacity.
abstract: The interplay between dietary habits and individual genetic make-up is assumed to influence risk of cancer, via modulation of DNA integrity. Our aim was to characterize internal and external factors that underlie inter-individual variability in DNA damage and repair and to identify dietary habits beneficial for maintaining DNA integrity. Habitual diet was estimated in 340 healthy individuals using a food frequency questionnaire and biomarkers of antioxidant status were quantified in fasting blood samples. Markers of DNA integrity were represented by DNA strand breaks, oxidized purines, oxidized pyrimidines and a sum of all three as total DNA damage. DNA repair was characterized by genetic variants and functional activities of base and nucleotide excision repair pathways. Sex, fruit-based food consumption and XPG genotype were factors significantly associated with the level of DNA damage. DNA damage was higher in women (p=0.035). Fruit consumption was negatively associated with the number of all measured DNA lesions, and this effect was mediated mostly by β-cryptoxanthin and β-tocopherol (p<0.05). XPG 1104His homozygotes appeared more vulnerable to DNA damage accumulation (p=0.001). Sex and individual antioxidants were also associated with DNA repair capacity; both the base and nucleotide excision repairs were lower in women and the latter increased with higher plasma levels of ascorbic acid and α-carotene (p<0.05). We have determined genetic and dietary factors that modulate DNA integrity. We propose that the positive health effect of fruit intake is partially mediated via DNA damage suppression and a simultaneous increase in DNA repair capacity.
authors.affiliation: Department of Molecular Biology of Cancer, Institute of Experimental Medicine ASCR, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address: j.slyskova@gmail.com.
authors.forename: Jana
authors.initials: J
authors.lastname: Slyskova
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Lorenzo
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Anette
authors.initials: A
authors.lastname: Karlsen
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Monica H
authors.initials: MH
authors.lastname: Carlsen
authors.affiliation: Department of Gene Expressions, Institute of Biotechnology ASCR, Prague, Prague, Czech Republic.
authors.forename: Vendula
authors.initials: V
authors.lastname: Novosadova
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Oslo, Norway.
authors.forename: Rune
authors.initials: R
authors.lastname: Blomhoff
authors.affiliation: Department of Molecular Biology of Cancer, Institute of Experimental Medicine ASCR, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Vodicka
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address: a.r.collins@medisin.uio.no.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Collins
mesh_terms: D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics* / Q000378:metabolism; D005247:Feeding Behavior; D005260:Female; D059647:Gene-Environment Interaction; D005819:Genetic Markers; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009664:Norway; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D000975:Antioxidants; D004268:DNA-Binding Proteins; D004720:Endonucleases; D005819:Genetic Markers; D009687:Nuclear Proteins; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5
keywords: DNA damage; DNA repair capacity; Diet; Genetic polymorphisms; Molecular epidemiology study