Abstract
Population-based studies have reported significant associations between specific genetic polymorphisms and breast cancer susceptibility. A number of studies have demonstrated that common variants of genes involved in the DNA repair pathway act as low penetrance breast cancer susceptibility alleles. We aimed to investigate the association of single nucleotide polymorphisms (SNPs) in the DNA repair genes XRCC1, XRCC2 and XRCC3 and breast cancer in MASTOS, a population-based case–control study of 1,109 Cypriot women with breast cancer diagnosed between 40 and 70 years and 1,177 age-matched healthy controls. Five coding SNPs were genotyped including rs1799782, rs25489 and rs25487 in XRCC1, rs3218536 in XRCC2 and rs861539 in XRCC3. Homozygous XRCC1 280His carriers had an increased risk of breast cancer (odds ratio 4.68; 95% CI 1.01–21.7; P = 0.03). The XRCC2 188His allele was associated with a marginal protective effect for breast cancer (odds ratio 0.79; 95% CI 0.62–1.00; P = 0.05). No significant associations were observed between the other three SNPs and breast cancer. This study suggests that genetic variation in SNPs in XRCC1 and XRCC2 genes may influence breast cancer susceptibility.
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References
Parkin DM, Bray F, Ferlay J et al (2005) Global cancer statistics, 2002. CA Cancer J Clin 55(2):74–108
Oldenburg RA, Meijers-Heijboer H, Cornelisse CJ et al (2007) Genetic susceptibility for breast cancer: how many more genes to be found? Crit Rev Oncol Hematol 63(2):125–149
Hadjisavvas A, Charalambous E, Adamou A et al (2004) Hereditary breast and ovarian cancer in Cyprus: identification of a founder BRCA2 mutation. Cancer Genet Cytogenet 151(2):152–156
Loizidou M, Marcou Y, Anastasiadou V et al (2007) Contribution of BRCA1 and BRCA2 germline mutations to the incidence of early-onset breast cancer in Cyprus. Clin Genet 71(2):165–170
van Gent DC, Hoeijmakers JH, Kanaar R (2001) Chromosomal stability and the DNA double-stranded break connection. Nat Rev Genet 2(3):196–206
Berwick M, Vineis P (2000) Markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review. J Natl Cancer Inst 92:874–897
Vodicka P, Kumar R, Stetina R et al (2004) Genetic polymorphisms in DNA repair genes and possible links with DNA repair rate, chromosomal aberrations and single-strand breaks in DNA. Carcinogenesis 25:757–763
Thacker J, Zdzienicka MZ (2003) The mammalian XRCC genes: their roles in DNA repair and genetic stability. DNA Repair (Amst) 2(6):655–672
Caldecott KW (2003) XRCC1 and DNA strand break repair. DNA Repair (Amst) 2:955–969
O’Regan P, Wilson C, Townsend S et al (2001) XRCC2 is a nuclear RAD51-like protein required for damage-dependent RAD51 focus formation without the need for ATP binding. J Biol Chem 276:22148–22153
Bishop DK, Ear U, Bhattacharyya A et al (1998) Xrcc3 is required for assembly of Rad51 complexes in vivo. J Biol Chem 273:21482–21488
Hu JJ, Smith TR, Miller MS et al (2001) Amino acid substitutions variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. Carcinogenesis 22:917–922
Pharoah PDP, Antoniou A, Bobrow M et al (2002) Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet 31:33–36
Mohrenweiser HW, Jones IM (1998) Variation in DNA repair is a factor in cancer susceptibility: a paradigm for the promises and perils of individual and population risk estimation? Mutat Res 400:15–24
Kubota Y, Nash R, Klungland A et al (1996) Reconstitution of DNA base-excision repair with purified human proteins: interaction between DNA polymerase b and the XRCC1 protein. EMBO J 15:6662–6670
Pachkowski BF, Winkel S, Kubota Y et al (2006) XRCC1 genotype and breast cancer: functional studies and epidemiologic data show interactions between XRCC1 codon 280 His and smoking. Cancer Res 66(5):2860–2868
Breast Cancer Association Consortium (2006) Commonly studied single-nucleotide polymorphisms and breast cancer: results from the Breast Cancer Association Consortium. J Natl Cancer Inst 98(19):1382–1396
García-Closas M, Egan KM, Newcomb PA et al (2006) Polymorphisms in DNA double-strand break repair genes and risk of breast cancer: two population-based studies in USA and Poland, and meta-analyses. Hum Genet 119(4):376–388
Auranen A, Song H, Waterfall C et al (2005) Polymorphisms in DNA repair genes and epithelial ovarian cancer risk. Int J Cancer 117(4):611–618
Thyagarajan B, Anderson KE, Folsom AR et al (2006) No association between XRCC1 and XRCC3 gene polymorphisms and breast cancer risk: Iowa Women’s Health Study. Cancer Detect Prev 30(4):313–321
Kiyohara C, Takayama K, Nakanishi Y (2006) Association of genetic polymorphisms in the base excision repair pathway with lung cancer risk: a meta-analysis. Lung Cancer 54(3):267–283
Acknowledgments
We thank Rena Papachristoforou for her assistance in data collection. We also thank the patients and the healthy volunteers who participated in MASTOS without whom this research could not have been done. This work is supported by Cyprus Research Promotion Foundation (IPE) grants 0104/13 and 0104/17 and the Cyprus Institute of Neurology and Genetics.
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Loizidou, M.A., Michael, T., Neuhausen, S.L. et al. Genetic polymorphisms in the DNA repair genes XRCC1, XRCC2 and XRCC3 and risk of breast cancer in Cyprus. Breast Cancer Res Treat 112, 575–579 (2008). https://doi.org/10.1007/s10549-007-9881-4
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DOI: https://doi.org/10.1007/s10549-007-9881-4