Research article
Expression levels of uridine 5'-diphospho-glucuronosyltransferase genes in breast tissue from healthy women are associated with mammographic density
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* Corresponding author: Åslaug Helland Aslaug.Helland@rr-research.no
1 Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Montebello, NO-0310, Norway
2 Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, NO-0315, Norway
3 Biomedical Research Group, Department of Informatics, University of Oslo, Oslo, NO-0315, Norway
4 Centre for Cancer Biomedicine, University of Oslo, Oslo, NO-0315, Norway
5 Department of Radiology, Oslo University Hospital Radiumhospitalet, Oslo, NO-0310, Norway
6 Department of Radiology, University Hospital of North Norway, Tromsø, NO- 9038, Norway
7 Department. of Pathology, Vestfold Hospital, Halfdan Wilhelmsens Alle' 17, Tønsberg, NO-3103, Norway
8 Department of Radiology, Innlandet Hospital, Brummundal, NO-2381, Norway
9 Department of Radiology, Buskerud Hospital, Drammen, NO-3004, Norway
10 Department for Clinical Molecular Biology (EpiGen), Institute for Clinical Medicine, Akershus University Hospital, University of Oslo, Oslo, NO-0315, Norway
11 Department of Surgery, Akerhus University Hospital, Lørenskog, 1478, Norway
12 Department of Nutrition, School of Medicine, University of Oslo, Oslo, NO-0315, Norway
13 Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
14 Department of Oncology, Oslo University Hospital Radiumhospitalet, Oslo, NO-0310, Norway
Breast Cancer Research 2010, 12:R65 doi:10.1186/bcr2632
Published: 27 August 2010Abstract
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.