Breast Cancer Research and Treatment

, Volume 143, Issue 1, pp 181–187

Breast cancer susceptibility risk associations and heterogeneity by E-cadherin tumor tissue expression

  • Hisani N. Horne
  • Mark E. Sherman
  • Montserrat Garcia-Closas
  • Paul D. Pharoah
  • Fiona M. Blows
  • Xiaohong R. Yang
  • Stephen M. Hewitt
  • Catherine M. Conway
  • Jolanta Lissowska
  • Louise A. Brinton
  • Ludmila Prokunina-Olsson
  • Sarah-Jane Dawson
  • Carlos Caldas
  • Douglas F. Easton
  • Stephen J. Chanock
  • Jonine D. Figueroa
Epidemiology

DOI: 10.1007/s10549-013-2771-z

Cite this article as:
Horne, H.N., Sherman, M.E., Garcia-Closas, M. et al. Breast Cancer Res Treat (2014) 143: 181. doi:10.1007/s10549-013-2771-z

Abstract

E-cadherin is involved in cell–cell adhesion and epithelial-to-mesenchymal transitions. In cancers, loss or inactivation of E-cadherin is associated with epithelial cell proliferation and invasion. Here, we sought to determine, if risk associations for 18 breast cancer susceptibility single nucleotide polymorphisms (SNPs) differed by E-cadherin tumor tissue expression in the Polish Breast Cancer Study (PBCS), using data on 1,347 invasive breast cancer cases and 2,366 controls. E-cadherin expression (low/high) was assessed using immunohistochemical staining of tumor tissue microarrays. Replication data on 2,006 cases and 6,714 controls from the Study of Epidemiology and Risk Factors in Cancer Heredity was used to follow-up promising findings from PBCS. In PBCS, we found the rs11249433 SNP at the 1p11.2 locus to be more strongly associated with risk of E-cadherin low tumors (OR = 1.30, 95 % CI = 1.08–1.56) than with E-cadherin high tumors [OR = 1.06, 95 % CI = 0.95–1.18; case-only p-heterogeneity (p-het) = 0.05]. Findings in PBCS for rs11249433 were replicated in SEARCH. Combined analyses of the two datasets for SNP rs11249433 revealed significant heterogeneity by E-cadherin expression (combined case-only p-het = 0.004). Further, among carriers of rs11249433, the highest risk was seen for E-cadherin low tumors that were ER-positive and of lobular histology. Our results in two independent data sets suggest that rs11249433, which is located between the NOTCH2 and FCGR1B genes within the 1p11.2 locus, is more strongly associated with risk of breast tumors with low or absent E-cadherin expression, and suggest that evaluation of E-cadherin tumor tissue expression may be useful in clarifying breast cancer risk factor associations.

Keywords

E-cadherin Single nucleotide polymorphism (SNP) Genetics of risk 

Supplementary material

10549_2013_2771_MOESM1_ESM.docx (56 kb)
Supplementary material 1 (DOCX 56 kb)
10549_2013_2771_MOESM2_ESM.docx (19 kb)
Supplementary material 2 (DOCX 18 kb)
10549_2013_2771_MOESM3_ESM.docx (17 kb)
Supplementary material 3 (DOCX 17 kb)

Copyright information

© Springer Science+Business Media New York (outside the USA) 2013

Authors and Affiliations

  • Hisani N. Horne
    • 1
    • 8
  • Mark E. Sherman
    • 2
  • Montserrat Garcia-Closas
    • 3
    • 4
  • Paul D. Pharoah
    • 5
  • Fiona M. Blows
    • 5
  • Xiaohong R. Yang
    • 1
  • Stephen M. Hewitt
    • 6
  • Catherine M. Conway
    • 6
  • Jolanta Lissowska
    • 7
  • Louise A. Brinton
    • 1
  • Ludmila Prokunina-Olsson
    • 1
  • Sarah-Jane Dawson
    • 5
  • Carlos Caldas
    • 5
  • Douglas F. Easton
    • 5
  • Stephen J. Chanock
    • 1
  • Jonine D. Figueroa
    • 1
  1. 1.Division of Cancer Epidemiology and Genetics, National Cancer InstituteNational Institutes of HealthRockvilleUSA
  2. 2.Division of Cancer Prevention, National Cancer InstituteNational Institutes of HealthRockvilleUSA
  3. 3.Breast Cancer Breakthrough CentreLondonUK
  4. 4.Section of Epidemiology and GeneticsThe Institute of Cancer ResearchSuttonUK
  5. 5.Department of Oncology and Department of Public Health and Primary CareUniversity of CambridgeCambridgeUK
  6. 6.Laboratory of Pathology, National Cancer InstituteNational Institutes of HealthBethesdaUSA
  7. 7.Department of Cancer Epidemiology and PreventionM. Sklodowska-Curie Memorial Cancer Center and Institute of OncologyWarsawPoland
  8. 8.National Institutes of Health/NCI/DCEG/HREBBethesdaUSA

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