Variation in genes required for normal mitosis and risk of breast cancer

Janet E Olson, X. Wang, Ellen L Goode, V. S. Pankratz, Z. S. Fredericksen, R. A. Vierkant, P. D P Pharoah, James R Cerhan, Fergus J Couch

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The down-regulation of genes involved in normal cell division can cause aberrant mitoses and increased cell death. Surviving cells exhibit aneuploidy and/or polyploidy. Since mitotic disruption has been linked with tumor development and progression, alterations in the expression or activity of these mitotic regulators may contribute to breast tumor formation. We evaluated associations between common inherited variation in these genes and breast cancer risk. Two hundred and five tagging and candidate functional single nucleotide polymorphisms in 30 genes required for normal cell division were genotyped in 798 breast cancer cases and 843 controls from the Mayo Clinic breast cancer study. Two variants in EIF3A (rs10787899 and rs3824830; P < 0.01) and four variants in SART1 (rs660118, rs679581, rs754532, and rs735942; P trend ≤ 0.02) were significantly associated with an altered risk of breast cancer along with single variants in RRM2, PSCD3, C11orf51, CDC16, SNW1, MFAP1, and CDC2 (P < 0.05). Variation in both SART1 (P = 0.009) and EIF3A (P = 0.02) was also significant at the gene level. Analyses suggested that SART1 SNPs rs660118 and rs679581 accounted for the majority of the association of that gene with breast cancer. The observed associations between breast cancer risk and genetic variation in the SART1 and EIF3A genes that are required for maintenance of normal mitosis suggest a direct role for these genes in the development of breast cancer.

Original languageEnglish (US)
Pages (from-to)423-430
Number of pages8
JournalBreast Cancer Research and Treatment
Volume119
Issue number2
DOIs
StatePublished - Jan 2010

Fingerprint

Mitosis
Breast Neoplasms
Genes
Cell Division
Single Nucleotide Polymorphism
Polyploidy
Aneuploidy
Cell Death
Down-Regulation
Maintenance
Neoplasms

Keywords

  • Breast cancer
  • Epidemiology
  • Genetics
  • Mitosis
  • Risk

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Variation in genes required for normal mitosis and risk of breast cancer. / Olson, Janet E; Wang, X.; Goode, Ellen L; Pankratz, V. S.; Fredericksen, Z. S.; Vierkant, R. A.; Pharoah, P. D P; Cerhan, James R; Couch, Fergus J.

In: Breast Cancer Research and Treatment, Vol. 119, No. 2, 01.2010, p. 423-430.

Research output: Contribution to journalArticle

Olson, Janet E ; Wang, X. ; Goode, Ellen L ; Pankratz, V. S. ; Fredericksen, Z. S. ; Vierkant, R. A. ; Pharoah, P. D P ; Cerhan, James R ; Couch, Fergus J. / Variation in genes required for normal mitosis and risk of breast cancer. In: Breast Cancer Research and Treatment. 2010 ; Vol. 119, No. 2. pp. 423-430.
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