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Centrosome-related genes, genetic variation, and risk of breast cancer

  • Epidemiology
  • Published:
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Abstract

Centrosome amplification has been detected in premalignant lesions and in situ tumors in the breast and in over 70% of invasive breast tumors, and has been associated with aneuploidy and tumor development. Based on these observations, the contribution of commonly inherited genetic variation in candidate genes related to centrosome structure and function to breast cancer risk was evaluated in an association study. Seven-hundred and 82 single nucleotide polymorphisms (SNPs) from 101 centrosomal genes were analyzed in 798 breast cancer cases and 843 controls from the Mayo Clinic Breast Cancer Study to assess the association between these SNPs (both individually and combined) and risk of breast cancer in this population. Eleven SNPs out of 782 from six genes displayed associations with breast cancer risk (P < 0.01). Haplotypes in five genes also displayed significant associations with risk. A two SNP combination of rs10145182 in NIN and rs2134808 in the TUBG1 locus (P-interaction = 0.00001), suggested SNPs in mediators of microtubule nucleation from the centrosome contribute to breast cancer. Evaluation of the simultaneous significance of all SNPs in the centrosome pathway suggested that the centrosome pathway is highly enriched (P = 4.76 × 10−50) for SNPs that are associated with breast cancer risk. Collections of weakly associated genetic variants in the centrosome pathway, rather than individual highly significantly associated SNPs, may account for a putative role for the centrosome pathway in predisposition to breast cancer.

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References

  1. Sluder G (2005) Two-way traffic: centrosomes and the cell cycle. Nat Rev Mol Cell Biol 6(9):743–748

    Article  CAS  PubMed  Google Scholar 

  2. Lange BM, Gull K (1996) Structure and function of the centriole in animal cells: progress and questions. Trends Cell Biol 6(9):348–352

    Article  CAS  PubMed  Google Scholar 

  3. Fukasawa K (2007) Oncogenes and tumour suppressors take on centrosomes. Nat Rev Cancer 7(12):911–924

    Article  CAS  PubMed  Google Scholar 

  4. D’Assoro AB, Lingle WL, Salisbury JL (2002) Centrosome amplification and the development of cancer. Oncogene 21(40):6146–6153

    Article  PubMed  Google Scholar 

  5. Brinkley BR (2001) Managing the centrosome numbers game: from chaos to stability in cancer cell division. Trends Cell Biol 11(1):18–21

    Article  CAS  PubMed  Google Scholar 

  6. Marx J (2001) Cell biology. Do centrosome abnormalities lead to cancer? Science 292(5516):426–429

    Article  CAS  PubMed  Google Scholar 

  7. Wang X et al (2008) Association of genetic variation in genes implicated in the beta-catenin destruction complex with risk of breast cancer. Cancer Epidemiol Biomarkers Prev 17(8):2101–2108

    Article  CAS  PubMed  Google Scholar 

  8. Andersen JS et al (2003) Proteomic characterization of the human centrosome by protein correlation profiling. Nature 426(6966):570–574

    Article  CAS  PubMed  Google Scholar 

  9. Carlson CS et al (2004) Selecting a maximally informative set of single-nucleotide polymorphisms for association analyses using linkage disequilibrium. Am J Hum Genet 74(1):106–120

    Article  CAS  PubMed  Google Scholar 

  10. Oliphant A, et al (2002) BeadArray technology: enabling an accurate, cost-effective approach to high-throughput genotyping. Biotechniques. Suppl:56–58, 60–61

  11. Steemers FJ, Gunderson KL (2005) Illumina, Inc. Pharmacogenomics 6(7):777–782

    Google Scholar 

  12. Weir BS (1996) Genetic data analysis II: methods for discrete population genetic data. Sinauer Associates, Inc., Sunderland MA, pp 98–99

  13. Gabriel SB et al (2002) The structure of haplotype blocks in the human genome. Science 296(5576):2225–2229

    Article  CAS  PubMed  Google Scholar 

  14. Schaid DJ et al (2002) Score tests for association between traits and haplotypes when linkage phase is ambiguous. Am J Hum Genet 70(2):425–434

    Article  PubMed  Google Scholar 

  15. Chai HS et al (2009) GLOSSI: a method to assess the association of genetic loci-sets with complex diseases. BMC Bioinformatics 10:102

    Article  PubMed  Google Scholar 

  16. Kelemen LE et al (2009) Genetic variation in the chromosome 17q23 amplicon and breast cancer risk. Cancer Epidemiol Biomarkers Prev 18(6):1864–1868

    Article  CAS  PubMed  Google Scholar 

  17. Garcia-Closas M, et al (2008) Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics. PLoS Genet 4(4):e1000054

    Google Scholar 

  18. Guo HQ et al (2007) Analysis of the cellular centrosome in fine-needle aspirations of the breast. Breast Cancer Res 9(4):R48

    Article  PubMed  Google Scholar 

  19. Schneeweiss A et al (2003) Centrosomal aberrations in primary invasive breast cancer are associated with nodal status and hormone receptor expression. Int J Cancer 107(3):346–352

    Article  CAS  PubMed  Google Scholar 

  20. Ganem NJ, Godinho SA, Pellman D (2009) A mechanism linking extra centrosomes to chromosomal instability. Nature 460(7252):278–282

    Article  CAS  PubMed  Google Scholar 

  21. Baker DJ et al (2009) Whole chromosome instability caused by Bub1 insufficiency drives tumorigenesis through tumor suppressor gene loss of heterozygosity. Cancer Cell 16(6):475–486

    Article  CAS  PubMed  Google Scholar 

  22. LeRoy PJ et al (2007) Localization of human TACC3 to mitotic spindles is mediated by phosphorylation on Ser558 by Aurora A: a novel pharmacodynamic method for measuring Aurora A activity. Cancer Res 67(11):5362–5370

    Article  CAS  PubMed  Google Scholar 

  23. Delgehyr N, Sillibourne J, Bornens M (2005) Microtubule nucleation and anchoring at the centrosome are independent processes linked by ninein function. J Cell Sci 118(Pt 8):1565–1575

    Article  CAS  PubMed  Google Scholar 

  24. Stillwell EE, Zhou J, Joshi HC (2004) Human ninein is a centrosomal autoantigen recognized by CREST patient sera and plays a regulatory role in microtubule nucleation. Cell Cycle 3(7):923–930

    CAS  PubMed  Google Scholar 

  25. Thomas G et al (2009) A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1). Nat Genet 41(5):579–584

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was funded in part by a grant 5R01CA122340-02 and a Breast Cancer Specialized Program of Research Excellence (SPORE) grant P50CA166201 from the National Cancer Institute.

Conflicts of interest statement

None of the authors have a financial relationship with the organization that sponsored the research (NIH). We further state that we have full control of all primary data and that we agree to allow the journal to review our data if requested.

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Authors and Affiliations

  1. Mayo Clinic College of Medicine, Rochester, MN, USA

    J. E. Olson, X. Wang, V. S. Pankratz, Z. S. Fredericksen, C. M. Vachon, R. A. Vierkant, J. R. Cerhan & F. J. Couch

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  1. J. E. Olson
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  2. X. Wang
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  3. V. S. Pankratz
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  4. Z. S. Fredericksen
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  5. C. M. Vachon
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  6. R. A. Vierkant
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  7. J. R. Cerhan
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  8. F. J. Couch
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Correspondence to J. E. Olson.

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Olson, J.E., Wang, X., Pankratz, V.S. et al. Centrosome-related genes, genetic variation, and risk of breast cancer. Breast Cancer Res Treat 125, 221–228 (2011). https://doi.org/10.1007/s10549-010-0950-8

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  • DOI: https://doi.org/10.1007/s10549-010-0950-8

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