Dietary fat-dependent transcriptional architecture and copy number alterations associated with modifiers of mammary cancer metastasis

Ryan R. Gordon, Michele La Merrill, Kent W. Hunter, Peter Sørensen, David W. Threadgill, Daniel Pomp

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Breast cancer is a complex disease resulting from a combination of genetic and environmental factors. Among environmental factors, body composition and intake of specific dietary components like total fat are associated with increased incidence of breast cancer and metastasis. We previously showed that mice fed a high-fat diet have shorter mammary cancer latency, increased tumor growth and more pulmonary metastases than mice fed a standard diet. Subsequent genetic analysis identified several modifiers of metastatic mammary cancer along with widespread interactions between cancer modifiers and dietary fat. To elucidate diet-dependent genetic modifiers of mammary cancer and metastasis risk, global gene expression profiles and copy number alterations from mammary cancers were measured and expression quantitative trait loci (eQTL) identified. Functional candidate genes that colocalized with previously detected metastasis modifiers were identified. Additional analyses, such as eQTL by dietary fat interaction analysis, causality and database evaluations, helped to further refine the candidate loci to produce an enriched list of genes potentially involved in the pathogenesis of metastatic mammary cancer.

Original languageEnglish (US)
Pages (from-to)279-293
Number of pages15
JournalClinical and Experimental Metastasis
Volume27
Issue number5
DOIs
StatePublished - May 1 2010
Externally publishedYes

Keywords

  • Breast cancer
  • Causality
  • eQTL
  • High-fat diet
  • Tumors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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