Top

Published in:

01-01-2011 | Epidemiology

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

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

Published in: Breast Cancer Research and Treatment | Issue 1/2011

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.

Available only for authorised users

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

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

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

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

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

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

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):2101–2108CrossRefPubMed

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

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):106–120CrossRefPubMed

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

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):2225–2229CrossRefPubMed

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):425–434CrossRefPubMed

15.

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

16.

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

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

18.

Guo HQ et al (2007) Analysis of the cellular centrosome in fine-needle aspirations of the breast. Breast Cancer Res 9(4):R48CrossRefPubMed

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):346–352CrossRefPubMed

20.

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

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):475–486CrossRefPubMed

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):5362–5370CrossRefPubMed

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):1565–1575CrossRefPubMed

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):923–930PubMed

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):579–584CrossRefPubMed

Title: Centrosome-related genes, genetic variation, and risk of breast cancer
Authors: J. E. Olson
X. Wang
V. S. Pankratz
Z. S. Fredericksen
C. M. Vachon
R. A. Vierkant
J. R. Cerhan
F. J. Couch
Publication date: 01-01-2011
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2011
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-010-0950-8

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2011

Lack of association between HER2 codon 655 polymorphism and breast cancer susceptibility: meta-analysis of 22 studies involving 19,341 subjects

Phase I/II study of sorafenib with anastrozole in patients with hormone receptor positive aromatase inhibitor resistant metastatic breast cancer

No evidence of MMTV-like env sequences in specimens from the Australian Breast Cancer Family Study

Identification of genes associated with chemosensitivity to SAHA/taxane combination treatment in taxane-resistant breast cancer cells

Associations between mammographic density and serum and dietary cholesterol

Lack of an association between AURKA T91A polymorphisms and breast cancer: a meta-analysis involving 32,141 subjects

Keynote webinar | Spotlight on antibody–drug conjugates in cancer