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

Lookup NU author(s): Dr John Tyson, Dr Fiona Caple, Dr Alison Spiers, Brian Burtle, Professor Ann Daly, Dr Liz Williams, Professor John Edward Hesketh, Professor John Mathers

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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 by poly A/T insertion-deletion polymorphism in the XPC gene). NER capacity varied l l-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.


Publication metadata

Author(s): Tyson J, Caple F, Spiers A, Burtle B, Daly AK, Williams EA, Hesketh JE, Mathers JC

Publication type: Article

Publication status: Published

Journal: British Journal of Nutrition

Year: 2009

Volume: 101

Issue: 9

Pages: 1316-1323

Date deposited: 23/03/2011

ISSN (print): 0007-1145

ISSN (electronic): 1475-2662

Publisher: Cambridge University Press

URL: http://dx.doi.org/10.1017/S0007114508076265

DOI: 10.1017/S0007114508076265


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