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

  • Epidemiology
  • Published:
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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.

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Acknowledgments

We thank Drs Beata Peplonska and Neonila Szeszenia-Dabrowska of the Nofer Institute of Occupational Medicine (Lodz, Poland), Witold Zatonski of the Department of Cancer Epidemiology and Prevention, the M Sklodowska-Curie Cancer Center and Institute of Oncology (Warsaw, Poland), and Pei Chao and Michael Stagner from Information Management Services (Silver Spring, MD, USA), for their valuable contributions to the study. We also thank the participants, physicians, pathologists, nurses, and interviewers from participating centers in Poland for their efforts during field-work.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This research was supported by the Intramural Research Programs of the Division of Cancer Epidemiology and Genetics and Center for Cancer Research of the National Cancer Institute. M. Garcias-Closas is funded by the Breakthrough Breast Cancer Centre and the Institute of Cancer Research, London, UK. We acknowledge NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre.

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Authors and Affiliations

  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA

    Hisani N. Horne, Xiaohong R. Yang, Louise A. Brinton, Ludmila Prokunina-Olsson, Stephen J. Chanock & Jonine D. Figueroa

  2. Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, MD, USA

    Mark E. Sherman

  3. Breast Cancer Breakthrough Centre, London, UK

    Montserrat Garcia-Closas

  4. Section of Epidemiology and Genetics, The Institute of Cancer Research, Sutton, UK

    Montserrat Garcia-Closas

  5. Department of Oncology and Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

    Paul D. Pharoah, Fiona M. Blows, Sarah-Jane Dawson, Carlos Caldas & Douglas F. Easton

  6. Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Stephen M. Hewitt & Catherine M. Conway

  7. Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland

    Jolanta Lissowska

  8. National Institutes of Health/NCI/DCEG/HREB, 9609 Medical Center Drive, Rm 7E234 MSC 7234, Bethesda, MD, 20892-7234, USA

    Hisani N. Horne

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  1. Hisani N. Horne
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  2. Mark E. Sherman
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  3. Montserrat Garcia-Closas
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  9. Jolanta Lissowska
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  10. Louise A. Brinton
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  12. Sarah-Jane Dawson
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  13. Carlos Caldas
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Correspondence to Hisani N. Horne.

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Horne, H.N., Sherman, M.E., Garcia-Closas, M. et al. Breast cancer susceptibility risk associations and heterogeneity by E-cadherin tumor tissue expression. Breast Cancer Res Treat 143, 181–187 (2014). https://doi.org/10.1007/s10549-013-2771-z

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  • DOI: https://doi.org/10.1007/s10549-013-2771-z

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