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Carcinogenesis Advance Access published online on January 16, 2004
Carcinogenesis, doi:10.1093/carcin/bgh064
© 2004 by Oxford University Press
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© 2004 Oxford University Press

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

Genetic polymorphisms in DNA repair genes and possible links with DNA repair rates, chromosomal aberrations and singlestrand breaks in DNA

Pavel Vodicka 1*, Rajiv Kumar 2, Rudolf Stetina 3, Somali Sanyal 4, Pavel Soucek 5, Vincent Haufroid 6, Maria Dusinska 7, Miroslava Kuricova 7, Maria Zamecnikova 8, Ludovit Musak 9, Jana Buchancova 9, Hannu Norppa 10, Ari Hirvonen 10, Ludmila Vodickova 5, Alessio Naccarati 1, Zora Matousu 1, and Kari Hemminki 2

1 Inst. Exper. Med., Acad. Sci. Czech Rep., Prague, Czech Republic
2 Dept. Biosci. at Novum, Karolinska Institute, Huddinge, Sweden; German Cancer Institute, Heidelberg, FRG, Czech Rep.
3 Purkynje Military Medical Academy, Hradec Kralove, Czech Rep.
4 Dept. Biosci. at Novum, Karolinska Institute, Huddinge, Sweden
5 Natl. Inst. Publ. Health, Prague, Czech Rep.
6 Catholic University of Louvain, Louvain, Belgium
7 Inst. Prevent. Clin. Medicine, Bratislava, Slovak Rep.
8 Natl. Inst. Publ. Health, Bratislava, Slovak Rep.
9 Dept. Occup. Med., Med. Faculty in Martin, Martin, Slovak Rep.
10 Finnish Inst. Occup. Health, Helsinki, Finland

* Corresponding author. E-mail: pvodicka{at}biomed.cas.cz.

Received 6 October 2003 ; revised 25 November 2003 ; accepted 16 December 2003

Abstract

We analysed in a central European population, the association between genetic polymorphisms in genes coding for DNA repair enzymes XPD exon 23 (A/C; K751Q), XPG exon 15 (G/C; D1104H), XPC exon 15 (A/C; K939Q), XRCC1 exon 10 (G/A, R399Q) and XRCC3 exon 7 (C/T, T241M), and the levels of chromosomal aberrations (CAs) and singlestrand breaks (SSBs) in peripheral lymphocytes. In these individuals we also measured the irradiation-specific DNA repair rates and the repair rates of 8-oxoguanines. An elevated frequency of chromosomal aberrations was observed in individuals with XPD, exon 23 A allele (AA and AC) genotypes (F=3.6, P=0.028, ANOVA). In multifactorial analysis of variance, the XPD exon 23-polymorphism appeared as a major factor influencing chromosomal aberrations (F=4.2, P=0.017). Single-strand breaks in DNA, on the other hand, were modulated by XPD (F=4.3, P=0.023), XPG (F=4.3, P=0.024) and XRCC1 genotypes (F=3.0, P=0.064). Irradiation-specific DNA repair rates (reflecting mainly base-excision repair activity) were affected by XRCC1 (F=5.9, P=0.010) and XPC polymorphisms (F=4.2, P=0.046, MANOVA).

Our results from this study suggest that markers of genotoxicity are associated with polymorphisms in genes coding DNA repair enzymes.

Chromosomal aberrations, single-strand breaks, DNA repair rates, genetic polymorphisms in DNA repair genes
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