title: Comprehensive analysis of NuMA variation in breast cancer.
abstract: BACKGROUND
  A recent genome wide case-control association study identified NuMA region on 11q13 as a candidate locus for breast cancer susceptibility. Specifically, the variant Ala794Gly was suggested to be associated with increased risk of breast cancer.
  
  
  METHODS
  In order to evaluate the NuMa gene for breast cancer susceptibility, we have here screened the entire coding region and exon-intron boundaries of NuMa in 92 familial breast cancer patients and constructed haplotypes of the identified variants. Five missense variants were further screened in 341 breast cancer cases with a positive family history and 368 controls. We examined the frequency of Ala794Gly in an extensive series of familial (n = 910) and unselected (n = 884) breast cancer cases and controls (n = 906), with a high power to detect the suggested breast cancer risk. We also tested if the variant is associated with histopathologic features of breast tumors.
  
  
  RESULTS
  Screening of NuMA resulted in identification of 11 exonic variants and 12 variants in introns or untranslated regions. Five missense variants that were further screened in breast cancer cases with a positive family history and controls, were each carried on a unique haplotype. None of the variants, or the haplotypes represented by them, was associated with breast cancer risk although due to low power in this analysis, very low risk alleles may go unrecognized. The NuMA Ala794Gly showed no difference in frequency in the unselected breast cancer case series or familial case series compared to control cases. Furthermore, Ala794Gly did not show any significant association with histopathologic characteristics of the tumors, though Ala794Gly was slightly more frequent among unselected cases with lymph node involvement.
  
  
  CONCLUSIONS
  Our results do not support the role of NuMA variants as breast cancer susceptibility alleles.
authors.affiliation: Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland. outi.kilpivaara@helsinki.fi
authors.forename: Outi
authors.initials: O
authors.lastname: Kilpivaara
authors.forename: Matias
authors.initials: M
authors.lastname: Rantanen
authors.forename: Anitta
authors.initials: A
authors.lastname: Tamminen
authors.forename: Kristiina
authors.initials: K
authors.lastname: Aittomäki
authors.forename: Carl
authors.initials: C
authors.lastname: Blomqvist
authors.forename: Heli
authors.initials: H
authors.lastname: Nevanlinna
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D000483:Alleles; D034961:Antigens, Nuclear / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D020125:Mutation, Missense; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics*; D017354:Point Mutation; D012306:Risk
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins