Skewed X chromosome inactivation and early-onset breast cancer.
BACKGROUND
Skewed X chromosome inactivation may be more common in women with epithelial ovarian cancer and early-onset breast cancer. We tested this hypothesis in a group of 235 breast cancer patients and 253 controls (mean age 45.8 years) from a larger population based case control study.


METHODS
We measured X chromosome inactivation with the AR gene assay in lymphocyte DNA digested with the methylation specific enzyme HpaII. We judged skewness using an adjusted measure (relative to the undigested sample) with a cut point of 75%, and an unadjusted measure where skewed was defined as > 90% of the signal from one allele in the HpaII digested sample.


RESULTS
There were no significant differences in any of the skewing measures between cases and controls. Using the adjusted skewing measure among pre-menopausal subjects under the age of 50, 14% of cases versus 11% of controls were skewed, OR = 1.2, 95% CI 0.6 to 2.3; using the unadjusted measure, OR = 0.9, 95% CI 0.4 to 2.0.


CONCLUSIONS
While we cannot rule out a subtle difference of approximately twofold or less, we have failed to find a significant difference in the prevalence of skewed X chromosome inactivation in younger women with breast cancer compared to controls.
Struewing
J P
JP
Laboratory of Population Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. js140a@nih.gov
Pineda
M A
MA
Sherman
M E
ME
Lissowska
J
J
Brinton
L A
LA
Peplonska
B
B
Bardin-Mikolajczak
A
A
Garcia-Closas
M
M
D000328:Adult; D017668:Age of Onset; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D049951:X Chromosome Inactivation / Q000235:genetics*