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Breast Cancer Research
Published in: Breast Cancer Research 4/2010

Open Access 01-08-2010 | Research article

Expression levels of uridine 5'-diphospho-glucuronosyltransferase genes in breast tissue from healthy women are associated with mammographic density

Authors: Vilde D Haakensen, Margarethe Biong, Ole Christian Lingjærde, Marit Muri Holmen, Jan Ole Frantzen, Ying Chen, Dina Navjord, Linda Romundstad, Torben Lüders, Ida K Bukholm, Hiroko K Solvang, Vessela N Kristensen, Giske Ursin, Anne-Lise Børresen-Dale, Åslaug Helland

Published in: Breast Cancer Research | Issue 4/2010

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Abstract

Introduction

Mammographic density (MD), as assessed from film screen mammograms, is determined by the relative content of adipose, connective and epithelial tissue in the female breast. In epidemiological studies, a high percentage of MD confers a four to six fold risk elevation of developing breast cancer, even after adjustment for other known breast cancer risk factors. However, the biologic correlates of density are little known.

Methods

Gene expression analysis using whole genome arrays was performed on breast biopsies from 143 women; 79 women with no malignancy (healthy women) and 64 newly diagnosed breast cancer patients, both included from mammographic centres. Percent MD was determined using a previously validated, computerized method on scanned mammograms. Significance analysis of microarrays (SAM) was performed to identify genes influencing MD and a linear regression model was used to assess the independent contribution from different variables to MD.

Results

SAM-analysis identified 24 genes differentially expressed between samples from breasts with high and low MD. These genes included three uridine 5'-diphospho-glucuronosyltransferase (UGT) genes and the oestrogen receptor gene (ESR1). These genes were down-regulated in samples with high MD compared to those with low MD. The UGT gene products, which are known to inactivate oestrogen metabolites, were also down-regulated in tumour samples compared to samples from healthy individuals. Several single nucleotide polymorphisms (SNPs) in the UGT genes associated with the expression of UGT and other genes in their vicinity were identified.

Conclusions

Three UGT enzymes were lower expressed both in breast tissue biopsies from healthy women with high MD and in biopsies from newly diagnosed breast cancers. The association was strongest amongst young women and women using hormonal therapy. UGT2B10 predicts MD independently of age, hormone therapy and parity. Our results indicate that down-regulation of UGT genes in women exposed to female sex hormones is associated with high MD and might increase the risk of breast cancer.
Appendix
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Metadata
Title
Expression levels of uridine 5'-diphospho-glucuronosyltransferase genes in breast tissue from healthy women are associated with mammographic density
Authors
Vilde D Haakensen
Margarethe Biong
Ole Christian Lingjærde
Marit Muri Holmen
Jan Ole Frantzen
Ying Chen
Dina Navjord
Linda Romundstad
Torben Lüders
Ida K Bukholm
Hiroko K Solvang
Vessela N Kristensen
Giske Ursin
Anne-Lise Børresen-Dale
Åslaug Helland
Publication date
01-08-2010
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 4/2010
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2632

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