You are here

Article Text

Article menu
Download PDFPDF
Letters to JMG
High incidence of skewed X chromosome inactivation in young patients with familial non-BRCA1/BRCA2 breast cancer
  1. M Kristiansen1,
  2. G P S Knudsen1,
  3. P Maguire2,
  4. S Margolin3,
  5. J Pedersen1,
  6. A Lindblom2,
  7. K H Ørstavik4
  1. 1Faculty Division Rikshospitalet, University of Oslo, Oslo, Norway
  2. 2Department of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
  3. 3Department of Oncology, Karolinska University Hospital at Södersjukhuset, Stockholm, Sweden
  4. 4Department of Medical Genetics, Rikshospitalet, Oslo
  1. Correspondence to:
 Professor Karen Helene Ørstavik
 Department of Medical Genetics, Rikshospitalet, 0027 Oslo, Norway; k.h.orstavikmedisin.uio.no

Abstract

Background: A higher frequency of skewed X chromosome inactivation has been reported in a consecutive series of young patients with breast cancer compared with controls of a similar age.

Objective: To investigate the X inactivation pattern in patients with familial non-BRCA1/BRCA2 breast cancer (n = 272), BRCA1/BRCA2 germline mutations (n = 35), and sporadic breast cancer (n = 292).

Methods: X inactivation pattern was determined by polymerase chain reaction analysis of the highly polymorphic CAG repeat in the androgen receptor (AR) gene. The X inactivation pattern was classified as skewed when 90% or more of the cells preferentially expressed one X chromosome.

Results: Young patients with familial breast cancer had a significantly higher frequency of skewed X inactivation (11.2%) than young controls (2.7%) (p = 0.001). There was also a strong tendency for middle aged patients with sporadic breast cancer to be more skewed than middle aged controls (13.6% v 4.4%) (p = 0.02). No association between skewed X inactivation and breast cancer was found for the BRCA1/BRCA2 patients .

Conclusions: Skewed X inactivation may be a risk factor for the development of breast cancer in both sporadic and familial breast cancer and may indicate an effect of X linked genes.

  • familial breast cancer
  • sporadic breast cancer
  • X chromosome inactivation

https://doi.org/10.1136/jmg.2005.032433

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Footnotes

    • Competing interests: none declared