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.
- breast cancer
- skewed inactivation
- X chromosome
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Published Online First 27 May 2005
This work was supported by intramural funds and by Contract NCI N01-CP-91013 to the Maria Sklodowska-Curie Memorial Cancer Center and the Institute of Oncology from the Division of Cancer Epidemiology and Genetics, and by intramural funds from the Center for Cancer Research, NCI
Competing interests: none declared