title: Extent of differential allelic expression of candidate breast cancer genes is similar in blood and breast.
abstract: BACKGROUND
  Normal gene expression variation is thought to play a central role in inter-individual variation and susceptibility to disease. Regulatory polymorphisms in cis-acting elements result in the unequal expression of alleles. Differential allelic expression (DAE) in heterozygote individuals could be used to develop a new approach to discover regulatory breast cancer susceptibility loci. As access to large numbers of fresh breast tissue to perform such studies is difficult, a suitable surrogate test tissue must be identified for future studies.
  
  
  METHODS
  We measured differential allelic expression of 12 candidate genes possibly related to breast cancer susceptibility (BRCA1, BRCA2, C1qA, CCND3, EMSY, GPX1, GPX4, MLH3, MTHFR, NBS1, TP53 and TRXR2) in breast tissue (n = 40) and fresh blood (n = 170) of healthy individuals and EBV-transformed lymphoblastoid cells (n = 19). Differential allelic expression ratios were determined by Taqman assay. Ratio distributions were compared using t-test and Wilcoxon rank sum test, for mean ratios and variances respectively.
  
  
  RESULTS
  We show that differential allelic expression is common among these 12 candidate genes and is comparable between breast and blood (fresh and transformed lymphoblasts) in a significant proportion of them. We found that eight out of nine genes with DAE in breast and fresh blood were comparable, as were 10 out of 11 genes between breast and transformed lymphoblasts.
  
  
  CONCLUSIONS
  Our findings support the use of differential allelic expression in blood as a surrogate for breast tissue in future studies on predisposition to breast cancer.
authors.affiliation: Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre and Department of Oncology, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK. ana-teresa.maia@cancer.org.uk
authors.forename: Ana-Teresa
authors.initials: AT
authors.lastname: Maia
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Spiteri
authors.forename: Alvin J X
authors.initials: AJ
authors.lastname: Lee
authors.forename: Martin
authors.initials: M
authors.lastname: O'Reilly
authors.forename: Linda
authors.initials: L
authors.lastname: Jones
authors.forename: Carlos
authors.initials: C
authors.lastname: Caldas
authors.forename: Bruce A J
authors.initials: BA
authors.lastname: Ponder
mesh_terms: D000483:Alleles; D001402:B-Lymphocytes / Q000502:physiology*; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide