title: High incidence of skewed X chromosome inactivation in young patients with familial non-BRCA1/BRCA2 breast cancer.
abstract: BACKGROUND
  A higher frequency of skewed X chromosome inactivation has been reported in a consecutive series of young patients with breast cancer compared with controls of a similar age.
  
  
  OBJECTIVE
  To investigate the X inactivation pattern in patients with familial non-BRCA1/BRCA2 breast cancer (n = 272), BRCA1/BRCA2 germline mutations (n = 35), and sporadic breast cancer (n = 292).
  
  
  METHODS
  X inactivation pattern was determined by polymerase chain reaction analysis of the highly polymorphic CAG repeat in the androgen receptor (AR) gene. The X inactivation pattern was classified as skewed when 90% or more of the cells preferentially expressed one X chromosome.
  
  
  RESULTS
  Young patients with familial breast cancer had a significantly higher frequency of skewed X inactivation (11.2%) than young controls (2.7%) (p = 0.001). There was also a strong tendency for middle aged patients with sporadic breast cancer to be more skewed than middle aged controls (13.6% v 4.4%) (p = 0.02). No association between skewed X inactivation and breast cancer was found for the BRCA1/BRCA2 patients .
  
  
  CONCLUSIONS
  Skewed X inactivation may be a risk factor for the development of breast cancer in both sporadic and familial breast cancer and may indicate an effect of X linked genes.
authors.forename: M
authors.initials: M
authors.lastname: Kristiansen
authors.forename: G P S
authors.initials: GP
authors.lastname: Knudsen
authors.forename: P
authors.initials: P
authors.lastname: Maguire
authors.forename: S
authors.initials: S
authors.lastname: Margolin
authors.forename: J
authors.initials: J
authors.lastname: Pedersen
authors.forename: A
authors.initials: A
authors.lastname: Lindblom
authors.forename: K H
authors.initials: KH
authors.lastname: Ørstavik
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D041321:Chromosomes, Human, X; D005192:Family Health; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D049951:X Chromosome Inactivation / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein