High incidence of skewed X chromosome inactivation in young patients with familial non-BRCA1/BRCA2 breast cancer.
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.
Kristiansen
M
M
Knudsen
G P S
GP
Maguire
P
P
Margolin
S
S
Pedersen
J
J
Lindblom
A
A
Ørstavik
K H
KH
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
D019313:BRCA1 Protein; D024682:BRCA2 Protein