Breast Cancer Research and Treatment

, 129:617

Evaluation of associations between common variation in mitotic regulatory pathways and risk of overall and high grade breast cancer

  • Kristen N. Stevens
  • Xianshu Wang
  • Zachary Fredericksen
  • V. Shane Pankratz
  • James Cerhan
  • Celine M. Vachon
  • Janet E. Olson
  • Fergus J. Couch
Brief Report

DOI: 10.1007/s10549-011-1587-y

Cite this article as:
Stevens, K.N., Wang, X., Fredericksen, Z. et al. Breast Cancer Res Treat (2011) 129: 617. doi:10.1007/s10549-011-1587-y

Abstract

Mitotic regulatory pathways insure proper timing of mitotic entry, sister chromatid cohesion and separation, and cytokinesis. Disruption of this process results in inappropriate chromosome segregation and aneuploidy, and appears to contribute to cancer. Specifically, disregulation and somatic mutation of mitotic regulators has been observed in human cancers, and overexpression of mitotic regulators is common in aggressive and late stage tumors. However, the role of germline variation in mitotic pathways and risk of cancer is not well understood. We tested 1,084 haplotype-tagging and functional variants from 164 genes in mitotic regulatory pathways in 791 Caucasian women with breast cancer and 843 healthy controls for association with risk of overall and high grade breast cancer. Sixty-one single nucleotide polymorphisms (SNPs) from 40 genes were associated (P < 0.05) with risk of breast cancer in a log-additive model. In addition, 60 SNPs were associated (P < 0.05) with risk of high grade breast cancer. However, none of these associations were significant after Bonferroni correction for multiple testing. In gene-level analyses, CDC25C, SCC1/RAD21, TLK2, and SMC6L1 were associated (P < 0.05) with overall breast cancer risk, CDC6, CDC27, SUMO3, RASSF1, KIF2, and CDC14A were associated with high grade breast cancer risk, and EIF3S10 and CDC25A were associated with both. Further investigation in breast and other cancers are needed to understand the influence of inherited variation in mitotic genes on tumor grade and cancer risk.

Keywords

Breast cancerGeneticsMitoticGrade

Supplementary material

10549_2011_1587_MOESM1_ESM.doc (574 kb)
Supplementary material 1 (DOC 574 kb)

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Kristen N. Stevens
    • 1
  • Xianshu Wang
    • 2
  • Zachary Fredericksen
    • 1
  • V. Shane Pankratz
    • 1
  • James Cerhan
    • 1
  • Celine M. Vachon
    • 1
  • Janet E. Olson
    • 1
  • Fergus J. Couch
    • 2
  1. 1.Department of Health Sciences ResearchMayo Clinic College of MedicineRochesterUSA
  2. 2.Department of Laboratory Medicine and PathologyMayo Clinic College of MedicineRochesterUSA