Journal Article

Polymorphisms in the DNA repair genes <i>XRCC1</i> and <i>ERCC2</i> and biomarkers of DNA damage in human blood mononuclear cells

Eric J. Duell, John K. Wiencke, Tsun-Jen Cheng, Andrea Varkonyi, Zheng Fa Zuo, Tara Devi S. Ashok, Eugene J. Mark, John C. Wain, David C. Christiani and Karl T. Kelsey

in Carcinogenesis

Volume 21, issue 5, pages 965-971
Published in print May 2000 | ISSN: 0143-3334
Published online May 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.5.965
Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells

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Polymorphisms in several DNA repair genes have recently been identified, but little is known about their phenotypic significance. To determine whether variation in DNA repair genes is related to host DNA damage, we studied the association between polymorphisms in XRCC1 (codon 399) and ERCC2 (codon 751) and two markers of DNA damage, sister chromatid exchange (SCE) frequencies (n = 76) and polyphenol DNA adducts (n = 61). SCE frequencies were determined using a modified fluorescence–Giemsa method and polyphenol DNA adducts were determined using a P1-enhanced 32P-post-labeling procedure. XRCC1 and ERCC2 genotypes were identified using PCR–RFLP. Mean SCE frequencies among current smokers who were homozygous carriers of the 399Gln allele in XRCC1 were greater than those in 399Arg/Arg current smokers. We also observed a possible gene-dosage effect for XRCC1 399Gln and detectable DNA adducts, and significantly more adducts among older subjects who were carriers of the 399Gln allele than in younger subjects with the 399Arg/Arg genotype. The polymorphism in ERCC2 was unrelated to SCE frequency or DNA adduct level. Our results suggest that carriers of the polymorphic XRCC1 399Gln allele may be at greater risk for tobacco- and age-related DNA damage.

Keywords: BER, base excision repair; ERCC2, excision repair cross-complementing group 2; NER, nucleotide excision repair; PARP, poly(ADP-ribose) polymerase; SCE, sister chromatid exchange; XRCC1, X-ray repair cross-complementing group 1.

Journal Article.  5529 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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