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DNA-repair genetic polymorphisms and risk of breast cancer in Cyprus

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

The DNA repair pathway is known to play a role in the etiology of breast cancer. A number of studies have demonstrated that common germline variants in genes involved in the DNA repair pathway influence breast cancer risk. To assess whether alterations in DNA repair genes contribute to breast cancer, we genotyped 12 single nucleotide polymorphisms (SNPs) in 1,109 Cypriot women with breast cancer and 1,177 age-matched healthy controls. We found significant associations with breast cancer for SNPs in the BRCA2 and MRE11A genes. Carriers of the BRCA2 rs1799944 variant (991 Asp) were found to have an increased risk of breast cancer (OR = 1.41, 95% CI 1.08–1.83, P = 0.01) with P trend = 0.0076. Homozygous carriers of the MRE11A rs601341 A allele had an increased risk of breast cancer (OR = 1.36, 95% CI 1.08–1.71, P = 0.009) with P trend = 0.0087. This study suggests that genetic variants in BRCA2 and MRE11A are associated with breast cancer risk.

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References

  1. Parkin DM, Bray F, Ferlay J et al (2005) Global cancer statistics, 2002. CA Cancer J Clin 55(2):74–108

    Article  PubMed  Google Scholar 

  2. Hamosh A, Scott AF, Amberger JS et al (2005) Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res 33(Database issue):D514–D517. doi:10.1093/nar/gki033

    Article  PubMed  CAS  Google Scholar 

  3. Walsh T, King MC (2007) Ten genes for inherited breast cancer. Cancer Cell 11(2):103–105. doi:10.1016/j.ccr.2007.01.010

    Article  PubMed  CAS  Google Scholar 

  4. Bau DT, Mau YC, Ding SL et al (2007) DNA double-strand break repair capacity and risk of breast cancer. Carcinogenesis 28(8):1726–1730. doi:10.1093/carcin/bgm109

    Article  PubMed  CAS  Google Scholar 

  5. Kennedy DO, Agrawal M, Shen J et al (2005) DNA repair capacity of lymphoblastoid cell lines from sisters discordant for breast cancer. J Natl Cancer Inst 97(2):127–132

    PubMed  CAS  Google Scholar 

  6. 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. doi:10.1016/j.critrevonc.2006.12.004

    Article  PubMed  CAS  Google Scholar 

  7. Goode EL, Ulrich CM, Potter JD (2002) Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev 11(12):1513–1530

    PubMed  CAS  Google Scholar 

  8. Kuschel B, Auranen A, McBride S et al (2002) Variants in DNA double-strand break repair genes and breast cancer susceptibility. Hum Mol Genet 11(12):1399–1407. doi:10.1093/hmg/11.12.1399

    Article  PubMed  CAS  Google Scholar 

  9. 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. doi:10.1007/s00439-006-0135-z

    Article  PubMed  CAS  Google Scholar 

  10. Haiman CA, Hsu C, de Bakker PI et al (2008) Comprehensive association testing of common genetic variation in DNA repair pathway genes in relationship with breast cancer risk in multiple populations. Hum Mol Genet 17(6):825–834. doi:10.1093/hmg/ddm354

    Article  PubMed  CAS  Google Scholar 

  11. Loizidou MA, Michael T, Neuhausen SL, Newbold RF, Marcou Y, Kakouri E et al (2008) Genetic polymorphisms in the DNA repair genes XRCC1, XRCC2 and XRCC3 and risk of breast cancer in Cyprus. Breast Cancer Res Treat. Epub ahead of print. doi:10.1007/s10549-007-9881-4

  12. International HapMap Consortium (2005) A haplotype map of the human genome. Nature 437(7063):1299–1320. doi:10.1038/nature04226

    Article  CAS  Google Scholar 

  13. Pharoah PDP, Antoniou A, Bobrow M et al (2002) Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet 31:33–36. doi:10.1038/ng853

    Article  PubMed  CAS  Google Scholar 

  14. 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. doi:10.1016/S0027-5107(98)00059-1

    PubMed  CAS  Google Scholar 

  15. Rapakko K, Heikkinen K, Karppinen SM et al (2006) Screening for RAD51 and BRCA2 BRC repeat mutations in breast and ovarian cancer families. Cancer Lett 236(1):142–147. doi:10.1016/j.canlet.2005.05.032

    Article  PubMed  CAS  Google Scholar 

  16. Breast Cancer Information Core Database (BIC) http://research.nhgri.nih.gov/bic/

  17. Fackenthal JD, Sveen L, Gao Q et al (2005) Complete allelic analysis of BRCA1 and BRCA2 variants in young Nigerian breast cancer patients. J Med Genet 42(3):276–281. doi:10.1136/jmg.2004.020446

    Article  PubMed  CAS  Google Scholar 

  18. Debniak T, Scott RJ, Górski B et al (2008) Common variants of DNA repair genes and malignant melanoma. Eur J Cancer 44(1):110–114. doi:10.1016/j.ejca.2007.10.006

    Article  PubMed  CAS  Google Scholar 

  19. Freedman ML, Penney KL, Stram DO et al (2004) Common variation in BRCA2 and breast cancer risk: a haplotype-based analysis in the Multiethnic Cohort. Hum Mol Genet 13(20):2431–2441. doi:10.1093/hmg/ddh270

    Article  PubMed  CAS  Google Scholar 

  20. 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. doi:10.1016/j.cancergencyto.2003.09.020

    Article  PubMed  CAS  Google Scholar 

  21. 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. doi:10.1111/j.1399-0004.2007.00747.x

    Article  PubMed  CAS  Google Scholar 

  22. van den Bosch M, Bree RT, Lowndes NF et al (2003) The MRN complex: coordinating and mediating the response to broken chromosomes. EMBO Rep 4(9):844–849. doi:10.1038/sj.embor.embor925

    Article  PubMed  CAS  Google Scholar 

  23. Rollinson S, Kesby H, Morgan GJ (2006) Haplotypic variation in MRE11, RAD50 and NBS1 and risk of non-Hodgkin’s lymphoma. Leuk Lymphoma 47(12):2567–2583. doi:10.1080/10428190600909743

    Article  PubMed  CAS  Google Scholar 

  24. 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

    Article  Google Scholar 

Download references

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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Authors and Affiliations

  1. Department of Electron Microscope/Molecular Pathology, The Cyprus Institute of Neurology and Genetics, 6, International Airport Ave., Ayios Dometios, P.O. Box 23462, 1683, Nicosia, Cyprus

    Maria A. Loizidou, Thalia Michael, Andreas Hadjisavvas & Kyriacos Kyriacou

  2. Department of Epidemiology, School of Medicine, University of California Irvine, Irvine, CA, 92697-7550, USA

    Susan L. Neuhausen

  3. Brunel Institute of Cancer Genetics and Pharmacogenomics, Faculty of Life Sciences, Brunel University, Uxbridge, United Kingdom

    Robert F. Newbold

  4. Bank of Cyprus Oncology Center, Nicosia, Cyprus

    Yiola Marcou, Eleni Kakouri, Maria Daniel & Panayiotis Papadopoulos

  5. Department of Oncology, Limassol General Hospital, Limassol, Cyprus

    Simos Malas

Authors
  1. Maria A. Loizidou
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  2. Thalia Michael
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  3. Susan L. Neuhausen
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  4. Robert F. Newbold
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  5. Yiola Marcou
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  6. Eleni Kakouri
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  7. Maria Daniel
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  8. Panayiotis Papadopoulos
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  9. Simos Malas
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  10. Andreas Hadjisavvas
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  11. Kyriacos Kyriacou
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Correspondence to Andreas Hadjisavvas.

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Loizidou, M.A., Michael, T., Neuhausen, S.L. et al. DNA-repair genetic polymorphisms and risk of breast cancer in Cyprus. Breast Cancer Res Treat 115, 623–627 (2009). https://doi.org/10.1007/s10549-008-0084-4

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  • DOI: https://doi.org/10.1007/s10549-008-0084-4

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