Also in the Oct. 28 JNCI( Skewed X Inactivation in BRCA1 Muta...),Health
Skewed X Inactivation in BRCA1 Mutation Carriers
One X chromosome is more frequently silenced than the other X chromosome in women who carry mutations in the BRCA1 gene, and the skewed X inactivation is associated with a later onset of breast or ovarian cancer in these women.
Each cell in a woman's body carries two X chromosomes, while those of a man carry only one X chromosome. To compensate for the extra X chromosome, the cells in a woman's body inactivate one of the chromosomes. The inactivation occurs during embryogenesis and usually occurs randomly so that each X chromosome will be inactivated with equal frequency in a blood sample from an adult woman. Previous research suggested that X inactivation may not occur randomly in women with ovarian or breast cancer.
To learn whether X inactivation is skewed in favor of one of the two X chromosomes in women with breast or ovarian cancer, Amanda Spurdle, Ph.D., of the Queensland Institute of Medical Research in Brisbane, Australia, and colleagues tested blood samples from 735 healthy control subjects, 313 ovarian cancer patients, 235 women with familial breast cancer who did not have a BRCA1 or BRCA2 gene mutation, and 323 unaffected and affected women with a BRCA1 or BRCA2 gene mutation.
The investigators found that skewed X inactivation was more common in women with BRCA1 gene mutations, and possibly in women with BRCA2 gene mutations, than in healthy control subjects. The trend was strongest in mutation carriers who did not have breast or ovarian cancer. In addition, skewed X inactivation was associated with an older age at diagnosis of breast or ovarian cancer.
"We propose that skewed X inactivation arises as a mechanism to favor expression of an X-linked allele that protects against cancer and that skewed X inactivation may be exacerbated in BRCA1 mutation carriers due to BRCA1 mutationrelated overexpression of X-linked genes," the authors write.
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