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Abstract

Title: Skewed X-chromosome inactivation and early-onset breast cancer.
Author: Struewing JP, Pineda MA, Sherman ME, Lissowska J, Brinton LA, Peplonska B, Bardin-Mikolajczak A, Garcia-Closas M
Journal: J Med Genet
Year: 2005
Month: May

Abstract: INTRODUCTION: Skewed or non-random 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 cases and 253 controls (mean age 45.8 years, s.e. 0.25) from a larger population-based case-control study conducted in Poland. METHODS: We measured X-chromosome inactivation in lymphocyte DNA digested with the methylation-specific enzyme HpaII using an assay for the polymorphic trinucleotide repeats in the AR gene. We considered a sample as skewed using an adjusted measure (relative to the undigested sample) with a cut-point of 75%, and an unadjusted measure where skewed was defined as more than 90% of the signal from one allele in the HpaII digested sample. Odds ratios (OR) and 95% confidence intervals (CI) estimated with logistic regression models were used as a measure of risk for categorical variables. We also used non-parametric Wilcoxon rank-sum and median statistics to compare continuous measures of skewing. RESULTS: There were no significant differences in any of the skewing measures between cases and controls, both within the entire sample set and among the 360 pre-menopausal women below age 50. Using the adjusted skewing measure among pre-menopausal subjects under age 50, 14% of cases versus 11% of controls were skewed, OR = 1.2, 95% CI 0.6 - 2.3; using the unadjusted measure, OR = 0.9, 95% CI 0.4 - 2.0. CONCLUSIONS: While we cannot rule out a subtle difference of approximately 2-fold 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.