British Journal of Nutrition

Full Papers

Molecular Nutrition

Inter-individual variation in nucleotide excision repair in young adults: effects of age, adiposity, micronutrient supplementation and genotype

John Tysona1a2 c1, Fiona Caplea1a3a6, Alison Spiersa1a2, Brian Burtlea3, Ann K. Dalya4, Elizabeth A. Williamsa5, John E. Hesketha1a3 and John C. Mathersa1a2

a1 Human Nutrition Research Centre, Newcastle University, Newcastle upon Tyne NE2 4HH, UK

a2 School of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK

a3 Institute for Cell and Molecular Biosciences, Newcastle upon Tyne NE2 4HH, UK

a4 School of Clinical Laboratory Sciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK

a5 Human Nutrition Unit, School of Medicine & Biomedical Sciences, University of Sheffield, Sheffield S10 2JX, UK

a6 School of Applied Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK

Abstract

Nucleotide excision repair (NER) is responsible for repairing bulky helix-distorting DNA lesions and is essential for the maintenance of genomic integrity. Severe hereditary impairment of NER leads to cancers such as those in xeroderma pigmentosum, and more moderate reductions in NER capacity have been associated with an increased cancer risk. Diet is a proven modifier of cancer risk but few studies have investigated the potential relationships between diet and NER. In the present study, the plasmid-based host cell reactivation assay was used to measure the NER capacity in peripheral blood mononuclear cells from fifty-seven volunteers aged 18–30 years before and after 6 weeks of supplementation with micronutrients (selenium and vitamins A, C and E). As a control, nine individuals remained unsupplemented over the same period. Volunteers were genotyped for the following polymorphisms in NER genes: ERCC5 Asp1104His (rs17655); XPC Lys939Gln (rs2228001); ERCC2 Lys751Gnl (rs13181); XPC PAT (an 83 bp poly A/T insertion–deletion polymorphism in the XPC gene). NER capacity varied 11-fold between individuals and was inversely associated with age and endogenous DNA strand breaks. For the first time, we observed an inverse association between adiposity and NER. No single polymorphism was associated with the NER capacity, although significant gene–gene interactions were observed between XPC Lys939Gln and ERCC5 Asp1104His and XPC Lys939Gln and ERCC2 Lys751Gnl. While there was no detectable effect of micronutrient supplementation on NER capacity, there was evidence that the effect of fruit intake on the NER capacity may be modulated by the ERCC2 Lys751Gnl single nucleotide polymorphism.

(Received April 23 2008)

(Revised August 14 2008)

(Accepted August 15 2008)

(Online publication October 07 2008)

Correspondence:

c1 Corresponding author: Dr John Tyson, fax +44 191 222 7914, email john.tyson@ncl.ac.uk

Footnotes

Abbreviations: BER, base excision repair; DART, Dietary Antioxidant Repair Trial; HCR, host cell reactivation; NER, nucleotide excision repair; PBMC, peripheral blood mononuclear cells; SNP, single nucleotide polymorphism; Tris, 2-amino-2-hydroxymethyl-propane-1,3-diol