Skewed X chromosome inactivation and early-onset breast cancer

Jeffrey P. Struewing, M. A. Pineda, Mark E. Sherman, J. Lissowska, L. A. Brinton, B. Peplonska, A. Bardin-Mikolajczak, M. Garcia-Closas

Research output: Contribution to journalArticle

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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 Hpall. 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 Hpall 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.

Original languageEnglish (US)
Pages (from-to)48-53
Number of pages6
JournalJournal of Medical Genetics
Volume43
Issue number1
DOIs
StatePublished - Jan 2006

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X Chromosome Inactivation
Breast Neoplasms
Methylation
Case-Control Studies
Alleles
Lymphocytes
DNA
Enzymes
Population
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Struewing, J. P., Pineda, M. A., Sherman, M. E., Lissowska, J., Brinton, L. A., Peplonska, B., ... Garcia-Closas, M. (2006). Skewed X chromosome inactivation and early-onset breast cancer. Journal of Medical Genetics, 43(1), 48-53. https://doi.org/10.1136/jmg.2005.033134

Skewed X chromosome inactivation and early-onset breast cancer. / Struewing, Jeffrey P.; Pineda, M. A.; Sherman, Mark E.; Lissowska, J.; Brinton, L. A.; Peplonska, B.; Bardin-Mikolajczak, A.; Garcia-Closas, M.

In: Journal of Medical Genetics, Vol. 43, No. 1, 01.2006, p. 48-53.

Research output: Contribution to journalArticle

Struewing, JP, Pineda, MA, Sherman, ME, Lissowska, J, Brinton, LA, Peplonska, B, Bardin-Mikolajczak, A & Garcia-Closas, M 2006, 'Skewed X chromosome inactivation and early-onset breast cancer', Journal of Medical Genetics, vol. 43, no. 1, pp. 48-53. https://doi.org/10.1136/jmg.2005.033134
Struewing JP, Pineda MA, Sherman ME, Lissowska J, Brinton LA, Peplonska B et al. Skewed X chromosome inactivation and early-onset breast cancer. Journal of Medical Genetics. 2006 Jan;43(1):48-53. https://doi.org/10.1136/jmg.2005.033134
Struewing, Jeffrey P. ; Pineda, M. A. ; Sherman, Mark E. ; Lissowska, J. ; Brinton, L. A. ; Peplonska, B. ; Bardin-Mikolajczak, A. ; Garcia-Closas, M. / Skewed X chromosome inactivation and early-onset breast cancer. In: Journal of Medical Genetics. 2006 ; Vol. 43, No. 1. pp. 48-53.
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