RGD Reference Report - Association of genetic variation in mitotic kinases with breast cancer risk. - Rat Genome Database

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

Authors: Wang, X  Fredericksen, ZS  Vierkant, RA  Kosel, ML  Pankratz, VS  Cerhan, JR  Justenhoven, C  Brauch, H  Olson, JE  Couch, FJ  Couch, FJ 
Citation: Wang X, etal., Breast Cancer Res Treat. 2010 Jan;119(2):453-62. doi: 10.1007/s10549-009-0404-3. Epub 2009 Apr 30.
RGD ID: 7495825
Pubmed: PMID:19404734   (View Abstract at PubMed)
PMCID: PMC2796295   (View Article at PubMed Central)
DOI: DOI:10.1007/s10549-009-0404-3   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Breast Neoplasms susceptibilityIAGP 7495825DNA:SNP and haplotypeRGD 
Breast Neoplasms susceptibilityISOMAP2K4 (Homo sapiens)7495825; 7495825DNA:SNP and haplotypeRGD 

Objects Annotated

Genes (Rattus norvegicus)
Map2k4  (mitogen activated protein kinase kinase 4)

Genes (Mus musculus)
Map2k4  (mitogen-activated protein kinase kinase 4)

Genes (Homo sapiens)
MAP2K4  (mitogen-activated protein kinase kinase 4)


Additional Information