title: Genetic variation in the major mitotic checkpoint genes does not affect familial breast cancer risk.
abstract: Aneuploidy, an aberrant number of chromosomes, is a very common characteristic of many types of cancers, including tumors of the breast. There is increasing evidence that defects in the spindle assembly checkpoint, which controls correct chromosome segregation between two daughter cells, might contribute to tumorigenesis. In the present study we examined the effect of promoter and coding single nucleotide polymorphisms (SNPs) in six major spindle checkpoint genes (BUB1B, BUB3, CENPE, MAD2L1, MAD2L2, TTK) on familial breast cancer (BC) risk. A case-control study was carried out with a total of nine SNPs using 441 German, familial BC cases and 552 controls matched by age, ethnicity and geographical region. Neither the individual SNPs in the studied genes nor the haplotypes in the BUB1B, CENPE and TTK genes caused any significant effect on the risk of BC. We used the multifactor-dimensionality reduction method in order to identify gene-gene interactions among the six mitotic checkpoint genes, but no association was detected. Therefore, our results indicate that the investigated SNPs in the mitotic checkpoint genes do not affect the risk of familial BC.
authors.affiliation: Division of Molecular Genetic Epidemiology C050, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. A.Vaclavicek@dkfz.de
authors.forename: Annika
authors.initials: A
authors.lastname: Vaclavicek
authors.forename: Justo Lorenzo
authors.initials: JL
authors.lastname: Bermejo
authors.forename: Barbara
authors.initials: B
authors.lastname: Wappenschmidt
authors.forename: Alfons
authors.initials: A
authors.lastname: Meindl
authors.forename: Christian
authors.initials: C
authors.lastname: Sutter
authors.forename: Rita K
authors.initials: RK
authors.lastname: Schmutzler
authors.forename: Marion
authors.initials: M
authors.lastname: Kiechle
authors.forename: Peter
authors.initials: P
authors.lastname: Bugert
authors.forename: Barbara
authors.initials: B
authors.lastname: Burwinkel
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Asta
authors.initials: A
authors.lastname: Försti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D005260:Female; D018816:Genes, cdc; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D064246:Mad2 Proteins; D008297:Male; D008875:Middle Aged; D000075223:Poly-ADP-Ribose Binding Proteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011505:Protein-Tyrosine Kinases; D011506:Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D012307:Risk Factors
chemical_list: C489444:BUB3 protein, human; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C577697:MAD2L1 protein, human; C120552:MAD2L2 protein, human; D064246:Mad2 Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011506:Proteins; D012097:Repressor Proteins; C068688:centromere protein E; D011505:Protein-Tyrosine Kinases; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases; C075840:TTK protein, human