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Skewed X chromosome inactivation and early-onset breast cancer
  1. J P Struewing1,
  2. M A Pineda1,
  3. M E Sherman2,
  4. J Lissowska3,
  5. L A Brinton2,
  6. B Peplonska4,
  7. A Bardin-Mikolajczak3,
  8. M Garcia-Closas2
  1. 1Laboratory of Population Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
  2. 2Hormonal and Reproductive Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
  3. 3Division of Cancer Epidemiology and Prevention, Cancer Center and M. Sklodowska-Curie Institute of Oncology, Warsaw, Poland
  4. 4Department of Occupational and Environmental Epidemiology, Nofer Institute of Occupational Medicine, Łódź, Poland
  1. Correspondence to:
 Jeffery P Struewing
 Laboratory of Population Genetics, 41 Library Dr, Room D702, Bethesda, MD 20892-5060, USA; js140a{at}nih.gov

Abstract

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
  • epidemiology
  • skewed inactivation
  • X chromosome

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Footnotes

  • 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

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