ORIGINAL PAPER Polymorphisms of the XRCC1 and XPD Genes and Breast Cancer Risk: A Case-Control Study Lívia Kipikašová & Tomáš Wolaschka & Peter Bohuš & Helena Baumohlová & Juraj Bober & Jana Blažejová & Ladislav Mirossay & Marek Šarišský & Andrej Miroššay & Martina Čižmáriková & Dana Potočeková & Ján Mojžiš Received: 25 January 2008 / Accepted: 18 March 2008 / Published online: 16 April 2008 # Arányi Lajos Foundation 2008 Abstract The purpose of this case control study was to evaluate the role of X-ray repair cross-complementing group 1 (XRCC1) and xeroderma pigmentosum group D (XPD) genotypes as genetic indicators of susceptibility to breast cancer (BC). We analysed DNA samples from 114 breast cancer patients and 113 control subjects using polymerase chain reaction–restriction fragment length polymorphism. For the single nucleotide polymorphisms in XRCC1 exon 10 (Arg399Gln, G/A) and XPD exon 23 (Lys751Gln, A/C), no remarkable differences for genotype distribution and allele frequencies were observed between BC group and control group in the study. The genotype frequency for homozygote A/A in XPD exon 6 (Arg156Arg, C/A) were significantly different between BC and control groups (P <0.0001, odds ratio=2.14; 95% confidence inter- val 1.44–3.17). The data indicate a possible role for XPD (Arg156Arg, C/A) polymorphisms in BC susceptibility. Keywords Breast cancer susceptibility . DNA repair . XPD . XRCC1 Introduction Breast cancer (BC) is the most frequent cancer in women. It represents the second leading cause of cancer death among women [1]. It has been hypothesized that subtle functional deficiencies in highly conserved DNA repair processes resulting from polymorphic variation may increase genetic susceptibility to BC. Polymorphisms in DNA repair genes can impact protein function leading to genomic instability facilitated by growth stimulation and increased cancer risk [2]. DNA repair protein X-ray repair cross-complementing group 1 (XRCC1) is required for the efficient repair of DNA damage caused by ischemia-reperfusion, oxidative stress, and DNA methylating agents. Mutations in XRCC1 result in decreased genetic stability, including increased frequencies of spontaneous or induced chromosome trans- locations or deletions. Protein XRCC1 has no catalytic activity. However, three domains have been identified within XRCC1 which interact with enzymes and appear to play a pivotal role in base excision repair. Shen et al. [3] identified an amino acid substitution in regions of XRCC1, an arginine to glutamine change at codon 399 (G→A) in exon 10. A number of epidemiological studies have assessed the association of the XRCC1 polymorphism with cancer incidence [4, 5]. Several different complementation groups have been characterized whose protein products take part in the different steps of nucleotide excision repair. Among the repair proteins, the xeroderma pigmentosum group D Pathol. Oncol. Res. (2008) 14:131–135 DOI 10.1007/s12253-008-9034-z L. Kipikašová : T. Wolaschka : L. Mirossay : M. Šarišský : A. Miroššay : M. Čižmáriková : J. Mojžiš (*) Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, 040 11 Košice, Slovak Republic e-mail: jan.mojzis@upjs.sk P. Bohuš : H. Baumohlová Department of Pathology, University Hospital, Košice, Slovak Republic J. Bober : J. Blažejová 1st Surgery Department, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic D. Potočeková Department of Informatics, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic