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

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)181-187
Number of pages7
JournalBreast Cancer Research and Treatment
Volume143
Issue number1
DOIs
StatePublished - Jan 2014

Fingerprint

Cadherins
Breast Neoplasms
Neoplasms
Single Nucleotide Polymorphism
Heredity
Epithelial-Mesenchymal Transition
Cell Adhesion
Histology
Epidemiology
Epithelial Cells
Cell Proliferation
Staining and Labeling

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Breast cancer susceptibility risk associations and heterogeneity by E-cadherin tumor tissue expression. / Horne, Hisani N.; Sherman, Mark E.; Garcia-Closas, Montserrat; Pharoah, Paul D.; Blows, Fiona M.; Yang, Xiaohong R.; Hewitt, Stephen M.; Conway, Catherine M.; Lissowska, Jolanta; Brinton, Louise A.; Prokunina-Olsson, Ludmila; Dawson, Sarah Jane; Caldas, Carlos; Easton, Douglas F.; Chanock, Stephen J.; Figueroa, Jonine D.

In: Breast Cancer Research and Treatment, Vol. 143, No. 1, 01.2014, p. 181-187.

Research output: Contribution to journalArticle

Horne, HN, Sherman, ME, Garcia-Closas, M, Pharoah, PD, Blows, FM, Yang, XR, Hewitt, SM, Conway, CM, Lissowska, J, Brinton, LA, Prokunina-Olsson, L, Dawson, SJ, Caldas, C, Easton, DF, Chanock, SJ & Figueroa, JD 2014, 'Breast cancer susceptibility risk associations and heterogeneity by E-cadherin tumor tissue expression', Breast Cancer Research and Treatment, vol. 143, no. 1, pp. 181-187. https://doi.org/10.1007/s10549-013-2771-z
Horne, Hisani N. ; Sherman, Mark E. ; Garcia-Closas, Montserrat ; Pharoah, Paul D. ; Blows, Fiona M. ; Yang, Xiaohong R. ; Hewitt, Stephen M. ; Conway, Catherine M. ; Lissowska, Jolanta ; Brinton, Louise A. ; Prokunina-Olsson, Ludmila ; Dawson, Sarah Jane ; Caldas, Carlos ; Easton, Douglas F. ; Chanock, Stephen J. ; Figueroa, Jonine D. / Breast cancer susceptibility risk associations and heterogeneity by E-cadherin tumor tissue expression. In: Breast Cancer Research and Treatment. 2014 ; Vol. 143, No. 1. pp. 181-187.
@article{e6f18166606f49928b450adcbf0f2c80,
title = "Breast cancer susceptibility risk associations and heterogeneity by E-cadherin tumor tissue expression",
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, Genetics of risk, Single nucleotide polymorphism (SNP)",
author = "Horne, {Hisani N.} and Sherman, {Mark E.} and Montserrat Garcia-Closas and Pharoah, {Paul D.} and Blows, {Fiona M.} and Yang, {Xiaohong R.} and Hewitt, {Stephen M.} and Conway, {Catherine M.} and Jolanta Lissowska and Brinton, {Louise A.} and Ludmila Prokunina-Olsson and Dawson, {Sarah Jane} and Carlos Caldas and Easton, {Douglas F.} and Chanock, {Stephen J.} and Figueroa, {Jonine D.}",
year = "2014",
month = "1",
doi = "10.1007/s10549-013-2771-z",
language = "English (US)",
volume = "143",
pages = "181--187",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",
number = "1",

}

TY - JOUR

T1 - Breast cancer susceptibility risk associations and heterogeneity by E-cadherin tumor tissue expression

AU - Horne, Hisani N.

AU - Sherman, Mark E.

AU - Garcia-Closas, Montserrat

AU - Pharoah, Paul D.

AU - Blows, Fiona M.

AU - Yang, Xiaohong R.

AU - Hewitt, Stephen M.

AU - Conway, Catherine M.

AU - Lissowska, Jolanta

AU - Brinton, Louise A.

AU - Prokunina-Olsson, Ludmila

AU - Dawson, Sarah Jane

AU - Caldas, Carlos

AU - Easton, Douglas F.

AU - Chanock, Stephen J.

AU - Figueroa, Jonine D.

PY - 2014/1

Y1 - 2014/1

N2 - 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.

AB - 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.

KW - E-cadherin

KW - Genetics of risk

KW - Single nucleotide polymorphism (SNP)

UR - http://www.scopus.com/inward/record.url?scp=84892833965&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84892833965&partnerID=8YFLogxK

U2 - 10.1007/s10549-013-2771-z

DO - 10.1007/s10549-013-2771-z

M3 - Article

VL - 143

SP - 181

EP - 187

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 1

ER -