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PMID: 19404734 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Association of genetic variation in mitotic kinases with breast cancer risk.

Breast cancer research and treatment ·Vol. 119 ·No. 2 ·2010-01-00 ·Pages 453-62

Wang X, Fredericksen ZS, Vierkant RA, Kosel ML, Pankratz VS, Cerhan JR, Justenhoven C, Brauch H, GENICA Consortium, Olson JE, Couch FJ

Abstract

An RNAi-based functional screening of mitotic kinases in Drosophila recently identified a number of members of the kinome that are required for normal cell division. Depletion of these kinases resulted in a number of different mitotic abnormalities including spindle malformation, chromosome mis-segregation, centrosome amplification and failure of cytokinesis (Bettencourt-Dias et al. in Nature 432:980-987, 2004). Since mitotic defects are commonly observed in cancer cells, these kinases may contribute to tumor development and/or progression. To investigate whether common genetic variation in the mitotic kinases are associated with breast cancer risk, we genotyped 386 single nucleotide polymorphisms (SNPs) from 44 mitotic kinase genes, in 798 breast cancer cases and 843 unaffected controls from a clinic-based study. A total of 22 SNPs from 13 kinase genes displayed significant associations with breast cancer risk (P(trend) < or = 0.05), including two SNPs from FYN (rs6914091 and rs1465061) that remained of interest after accounting for multiple testing (q = 0.06). These associations were stronger when evaluating cases with estrogen and progesterone receptor positive tumors. In addition, haplotype-based tests identified significant associations with risk for common haplotypes of the MAST2 (P = 0.04) and MAP2K4 (P = 0.006) genes. Although requiring replication, these findings suggest that genetic polymorphisms in mitotic kinases that have been implicated in chromosome instability and aneuploidy may contribute to the development of breast cancer.

MeSH Terms
Breast Neoplasms/enzymology,epidemiology,genetics,pathology Case-Control Studies Female Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Gene Frequency Genetic Predisposition to Disease Haplotypes Humans Logistic Models Midwestern United States/epidemiology Mitosis/genetics Odds Ratio Polymorphism, Single Nucleotide Protein Kinases/genetics Risk Assessment Risk Factors
Chemicals
Protein Kinases
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Wang Xianshu
Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. wangx1@mayo.edu
Fredericksen Zachary S
Vierkant Robert A
Kosel Matthew L
Pankratz V Shane
Cerhan James R
Justenhoven Christina
Brauch Hiltrud
GENICA Consortium
Olson Janet E
Couch Fergus J
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Article Info
Journal
Breast cancer research and treatment
Abbr.
Breast Cancer Res Treat
ISSN
1573-7217
DOI
10.1007/s10549-009-0404-3
Email
wangx1@mayo.edu
Published
2010-01-00
Epub
2009-00-30
Pages
453-62
Language
English
Region
Netherlands
NLM ID
8111104
PMCID
PMC2796295
Subset
IM
Grants
NCI NIH HHS · R01 CA122340-02 · United States
NCI NIH HHS · P50 CA116201 · United States
NCI NIH HHS · R01 CA122340 · United States
NCI NIH HHS · 5R01CA122340-02 · United States
NCI NIH HHS · P50CA166201 · United States
NCI NIH HHS · P50 CA116201-020002 · United States
External Links
PubMed source DOI: 10.1007/s10549-009-0404-3 PMC Full Text View journal details
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