Carcinogenesis Advance Access originally published online on October 6, 2006
Carcinogenesis 2007 28(3):657-664; doi:10.1093/carcin/bgl187
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Association of DNA repair polymorphisms with DNA repair functional outcomes in healthy human subjects
1 Institute of Experimental Medicine, Videnska 1083, 14200, Academy of Sciences of the Czech Republic Prague, Czech Republic
2 Purkynje Military Medical Academy, Hradec Kralove Czech Republic
3 Center of Occupational Medicine, National Institute of Public Health Prague, Czech Republic
4 Division of Molecular Genetic Epidemiology, German Cancer Research Center Heidelberg, Germany
5 Department of Biosciences at Novum, Karolinska Institute Huddinge, Sweden
6 Department of Biology, University of Pisa Italy
7 Department of Medical Biology, Jessenius Medical Faculty, Comenius Univesity Martin Slovak Republic
8 Laboratory of Industrial Toxicology, Department of Clinical Medicine, Nephrology and Health Sciences, University of Parma Italy
*To whom correspondence should be addressed. Tel: +420 2 41062694; Fax: +420 2 41062782; Email: pvodicka{at}biomed.cas.cz
We investigated association between polymorphisms in DNA repair genes and the capacity to repair DNA damage induced by 
-irradiation and by base oxidation in a healthy population. Irradiation-specific DNA repair rates were significantly decreased in individuals with XRCC1 Arg399Gln homozygous variant genotype (0.45 ± 0.47 SSB/109 Da) than in those with wild-type genotype (1.10 ± 0.70 SSB/109 Da, P = 0.0006, Mann–Witney U-test). The capacity to repair oxidative DNA damage was significantly decreased among individuals with hOGG1 Ser326Cys homozygous variant genotype (0.37 ± 0.28 SSB/109 Da) compared to those with wild-type genotype (0.83 ± 0.79 SSB/109 Da, P = 0.008, Mann–Witney U-test). Investigation of genotype combinations showed that the increasing number of variant alleles for both XRCC1 Arg399Gln and APE1 Asn148Glu polymorphisms resulted in a significant decrease of irradiation-specific repair rates (P = 0.008, Kruskal–Wallis test). Irradiation-specific DNA repair rates also decreased with increasing number of variant alleles in XRCC1 Arg399Gln in combination with variant alleles for two other XRCC1 polymorphisms, Arg194Trp and Arg280His (P = 0.002 and P = 0.005, respectively; Kruskal–Wallis test). In a binary combination variant alleles of hOGG1 Ser326Cys and APE1 Asn148Glu polymorphisms were associated with a significant decrease in the capacity to repair DNA oxidative damage (P = 0.018, Kruskal–Wallis test). In summary, XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms seem to exert the predominant modulating effect on irradiation-specific DNA repair capacity and the capacity to repair DNA oxidative damage, respectively.
Abbreviations: BER, base excision DNA repair; SSB, single-strand breaks; SNP, single nucleotide polymorphism; PBL, peripheral blood lymphocytes
Received June 22, 2006; revised September 25, 2006; accepted September 27, 2006.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H Kehrer-Sawatzki and D N Cooper Mosaicism in sporadic neurofibromatosis type 1: variations on a theme common to other hereditary cancer syndromes? J. Med. Genet., October 1, 2008; 45(10): 622 - 631. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Dusinska and A. R. Collins The comet assay in human biomonitoring: gene-environment interactions Mutagenesis, May 1, 2008; 23(3): 191 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Landi, F. Gemignani, A. Naccarati, B. Pardini, P. Vodicka, L. Vodickova, J. Novotny, A. Forsti, K. Hemminki, F. Canzian, et al. Polymorphisms within micro-RNA-binding sites and risk of sporadic colorectal cancer Carcinogenesis, March 1, 2008; 29(3): 579 - 584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mechilli, A. Schinoppi, K. Kobos, A. T. Natarajan, and F. Palitti DNA repair deficiency and acetaldehyde-induced chromosomal alterations in CHO cells Mutagenesis, January 1, 2008; 23(1): 51 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. V. Breton, W. Zhou, M. L. Kile, E.A. Houseman, Q. Quamruzzaman, M. Rahman, G. Mahiuddin, and D. C. Christiani Susceptibility to arsenic-induced skin lesions from polymorphisms in base excision repair genes Carcinogenesis, July 1, 2007; 28(7): 1520 - 1525. [Abstract] [Full Text] [PDF]
|
|