Single nucleotide variants in metastasis-related genes are associated with breast cancer risk, by lymph node involvement and estrogen receptor status, in women with European and African ancestry

Michelle R. Roberts; Lara E. Sucheston-Campbell; Gary R. Zirpoli; Michael Higgins; Jo L. Freudenheim; Elisa V. Bandera; Christine B. Ambrosone; Song Yao

doi:10.1002/mc.22565

Single nucleotide variants in metastasis-related genes are associated with breast cancer risk, by lymph node involvement and estrogen receptor status, in women with European and African ancestry

Michelle R. Roberts
, Lara E. Sucheston-Campbell
, Gary R. Zirpoli
, Michael Higgins
, Jo L. Freudenheim
, Elisa V. Bandera
, Christine B. Ambrosone
, Song Yao

Department of Epidemiology and Environmental Health

Harvard University
Roswell Park Cancer Institute
SUNY Buffalo
Ohio State University
Massachusetts General Hospital
Rutgers - The State University of New Jersey, New Brunswick

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

Single nucleotide polymorphisms (SNPs) in pathways influencing lymph node (LN) metastasis and estrogen receptor (ER) status in breast cancer may partially explain inter-patient variability in prognosis. We examined 154 SNPs in 12 metastasis-related genes for associations with breast cancer risk, stratified by LN and ER status, in European-American (EA) and African-American (AA) women. Two-thousand six hundred and seventy-one women enrolled in the Women's Circle of Health Study were genotyped. Pathway analyses were conducted using the adaptive rank truncated product (ARTP) method, with p_ARTP ≤ 0.10 as significant. Multi-allelic risk scores were created for the ARTP-significant gene(s). Single-SNP and risk score associations were modeled using logistic regression, with false discovery rate (FDR) P-value adjustment. Although single-SNP associations were not significant at p_FDR < 0.05, several genes were significant in the ARTP analyses. In AA women, significant ARTP gene-level associations included CDH1 with LN+ (p_ARTP = 0.10; multi-allelic OR = 1.13, 95%CI 1.07–1.19, p_FDR = 0.0003) and SIPA1 with ER− breast cancer (p_ARTP = 0.10; multi-allelic OR = 1.16, 95%CI 1.02–1.31, p_FDR = 0.03). In EA women, MTA2 was associated with overall breast cancer risk (p_ARTP = 0.004), regardless of ER status, and with LN− disease (p_ARTP = 0.01). Also significant were SATB1 in ER− (p_ARTP = 0.03; multi-allelic OR = 1.12, 95%CI 1.05–1.20, p_FDR = 0.003) and KISS1 in LN− (p_ARTP = 0.10; multi-allelic OR = 1.18, 95%CI 1.08–1.29, p_FDR = 0.002) analyses. Among LN+ cases, significant ARTP associations were observed for SNAI1, CD82, NME1, and CTNNB1 (multi-allelic OR = 1.09, 95%CI 1.04–1.14, p_FDR = 0.001). Our findings suggest that variants in several metastasis genes may affect breast cancer risk by LN or ER status, although verification in larger studies is required.

Original language	English
Pages (from-to)	1000-1009
Number of pages	10
Journal	Molecular Carcinogenesis
Volume	56
Issue number	3
DOIs	https://doi.org/10.1002/mc.22565
State	Published - Mar 1 2017

Keywords

African-American
breast neoplasms
estrogen receptor
lymph nodes
single nucleotide polymorphism

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10.1002/mc.22565

Cite this

Roberts, M. R., Sucheston-Campbell, L. E., Zirpoli, G. R., Higgins, M., Freudenheim, J. L., Bandera, E. V., Ambrosone, C. B., & Yao, S. (2017). Single nucleotide variants in metastasis-related genes are associated with breast cancer risk, by lymph node involvement and estrogen receptor status, in women with European and African ancestry. Molecular Carcinogenesis, 56(3), 1000-1009. https://doi.org/10.1002/mc.22565

@article{1a241096742a4aada6942009b203ab28,

title = "Single nucleotide variants in metastasis-related genes are associated with breast cancer risk, by lymph node involvement and estrogen receptor status, in women with European and African ancestry",

abstract = "Single nucleotide polymorphisms (SNPs) in pathways influencing lymph node (LN) metastasis and estrogen receptor (ER) status in breast cancer may partially explain inter-patient variability in prognosis. We examined 154 SNPs in 12 metastasis-related genes for associations with breast cancer risk, stratified by LN and ER status, in European-American (EA) and African-American (AA) women. Two-thousand six hundred and seventy-one women enrolled in the Women's Circle of Health Study were genotyped. Pathway analyses were conducted using the adaptive rank truncated product (ARTP) method, with pARTP ≤ 0.10 as significant. Multi-allelic risk scores were created for the ARTP-significant gene(s). Single-SNP and risk score associations were modeled using logistic regression, with false discovery rate (FDR) P-value adjustment. Although single-SNP associations were not significant at pFDR < 0.05, several genes were significant in the ARTP analyses. In AA women, significant ARTP gene-level associations included CDH1 with LN+ (pARTP = 0.10; multi-allelic OR = 1.13, 95\%CI 1.07–1.19, pFDR = 0.0003) and SIPA1 with ER− breast cancer (pARTP = 0.10; multi-allelic OR = 1.16, 95\%CI 1.02–1.31, pFDR = 0.03). In EA women, MTA2 was associated with overall breast cancer risk (pARTP = 0.004), regardless of ER status, and with LN− disease (pARTP = 0.01). Also significant were SATB1 in ER− (pARTP = 0.03; multi-allelic OR = 1.12, 95\%CI 1.05–1.20, pFDR = 0.003) and KISS1 in LN− (pARTP = 0.10; multi-allelic OR = 1.18, 95\%CI 1.08–1.29, pFDR = 0.002) analyses. Among LN+ cases, significant ARTP associations were observed for SNAI1, CD82, NME1, and CTNNB1 (multi-allelic OR = 1.09, 95\%CI 1.04–1.14, pFDR = 0.001). Our findings suggest that variants in several metastasis genes may affect breast cancer risk by LN or ER status, although verification in larger studies is required.",

keywords = "African-American, breast neoplasms, estrogen receptor, lymph nodes, single nucleotide polymorphism",

author = "Roberts, \{Michelle R.\} and Sucheston-Campbell, \{Lara E.\} and Zirpoli, \{Gary R.\} and Michael Higgins and Freudenheim, \{Jo L.\} and Bandera, \{Elisa V.\} and Ambrosone, \{Christine B.\} and Song Yao",

note = "Publisher Copyright: {\textcopyright} 2016 Wiley Periodicals, Inc.",

year = "2017",

month = mar,

day = "1",

doi = "10.1002/mc.22565",

language = "English",

volume = "56",

pages = "1000--1009",

journal = "Molecular Carcinogenesis",

issn = "0899-1987",

publisher = "Wiley-Liss Inc.",

number = "3",

}

Roberts, MR, Sucheston-Campbell, LE, Zirpoli, GR, Higgins, M, Freudenheim, JL, Bandera, EV, Ambrosone, CB & Yao, S 2017, 'Single nucleotide variants in metastasis-related genes are associated with breast cancer risk, by lymph node involvement and estrogen receptor status, in women with European and African ancestry', Molecular Carcinogenesis, vol. 56, no. 3, pp. 1000-1009. https://doi.org/10.1002/mc.22565

Single nucleotide variants in metastasis-related genes are associated with breast cancer risk, by lymph node involvement and estrogen receptor status, in women with European and African ancestry. / Roberts, Michelle R.; Sucheston-Campbell, Lara E.; Zirpoli, Gary R. et al.
In: Molecular Carcinogenesis, Vol. 56, No. 3, 01.03.2017, p. 1000-1009.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Single nucleotide variants in metastasis-related genes are associated with breast cancer risk, by lymph node involvement and estrogen receptor status, in women with European and African ancestry

AU - Roberts, Michelle R.

AU - Sucheston-Campbell, Lara E.

AU - Zirpoli, Gary R.

AU - Higgins, Michael

AU - Freudenheim, Jo L.

AU - Bandera, Elisa V.

AU - Ambrosone, Christine B.

AU - Yao, Song

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Single nucleotide polymorphisms (SNPs) in pathways influencing lymph node (LN) metastasis and estrogen receptor (ER) status in breast cancer may partially explain inter-patient variability in prognosis. We examined 154 SNPs in 12 metastasis-related genes for associations with breast cancer risk, stratified by LN and ER status, in European-American (EA) and African-American (AA) women. Two-thousand six hundred and seventy-one women enrolled in the Women's Circle of Health Study were genotyped. Pathway analyses were conducted using the adaptive rank truncated product (ARTP) method, with pARTP ≤ 0.10 as significant. Multi-allelic risk scores were created for the ARTP-significant gene(s). Single-SNP and risk score associations were modeled using logistic regression, with false discovery rate (FDR) P-value adjustment. Although single-SNP associations were not significant at pFDR < 0.05, several genes were significant in the ARTP analyses. In AA women, significant ARTP gene-level associations included CDH1 with LN+ (pARTP = 0.10; multi-allelic OR = 1.13, 95%CI 1.07–1.19, pFDR = 0.0003) and SIPA1 with ER− breast cancer (pARTP = 0.10; multi-allelic OR = 1.16, 95%CI 1.02–1.31, pFDR = 0.03). In EA women, MTA2 was associated with overall breast cancer risk (pARTP = 0.004), regardless of ER status, and with LN− disease (pARTP = 0.01). Also significant were SATB1 in ER− (pARTP = 0.03; multi-allelic OR = 1.12, 95%CI 1.05–1.20, pFDR = 0.003) and KISS1 in LN− (pARTP = 0.10; multi-allelic OR = 1.18, 95%CI 1.08–1.29, pFDR = 0.002) analyses. Among LN+ cases, significant ARTP associations were observed for SNAI1, CD82, NME1, and CTNNB1 (multi-allelic OR = 1.09, 95%CI 1.04–1.14, pFDR = 0.001). Our findings suggest that variants in several metastasis genes may affect breast cancer risk by LN or ER status, although verification in larger studies is required.

AB - Single nucleotide polymorphisms (SNPs) in pathways influencing lymph node (LN) metastasis and estrogen receptor (ER) status in breast cancer may partially explain inter-patient variability in prognosis. We examined 154 SNPs in 12 metastasis-related genes for associations with breast cancer risk, stratified by LN and ER status, in European-American (EA) and African-American (AA) women. Two-thousand six hundred and seventy-one women enrolled in the Women's Circle of Health Study were genotyped. Pathway analyses were conducted using the adaptive rank truncated product (ARTP) method, with pARTP ≤ 0.10 as significant. Multi-allelic risk scores were created for the ARTP-significant gene(s). Single-SNP and risk score associations were modeled using logistic regression, with false discovery rate (FDR) P-value adjustment. Although single-SNP associations were not significant at pFDR < 0.05, several genes were significant in the ARTP analyses. In AA women, significant ARTP gene-level associations included CDH1 with LN+ (pARTP = 0.10; multi-allelic OR = 1.13, 95%CI 1.07–1.19, pFDR = 0.0003) and SIPA1 with ER− breast cancer (pARTP = 0.10; multi-allelic OR = 1.16, 95%CI 1.02–1.31, pFDR = 0.03). In EA women, MTA2 was associated with overall breast cancer risk (pARTP = 0.004), regardless of ER status, and with LN− disease (pARTP = 0.01). Also significant were SATB1 in ER− (pARTP = 0.03; multi-allelic OR = 1.12, 95%CI 1.05–1.20, pFDR = 0.003) and KISS1 in LN− (pARTP = 0.10; multi-allelic OR = 1.18, 95%CI 1.08–1.29, pFDR = 0.002) analyses. Among LN+ cases, significant ARTP associations were observed for SNAI1, CD82, NME1, and CTNNB1 (multi-allelic OR = 1.09, 95%CI 1.04–1.14, pFDR = 0.001). Our findings suggest that variants in several metastasis genes may affect breast cancer risk by LN or ER status, although verification in larger studies is required.

KW - African-American

KW - breast neoplasms

KW - estrogen receptor

KW - lymph nodes

KW - single nucleotide polymorphism

UR - https://www.scopus.com/pages/publications/84992497331

U2 - 10.1002/mc.22565

DO - 10.1002/mc.22565

M3 - Article

C2 - 27597141

AN - SCOPUS:84992497331

SN - 0899-1987

VL - 56

SP - 1000

EP - 1009

JO - Molecular Carcinogenesis

JF - Molecular Carcinogenesis

IS - 3

ER -

Single nucleotide variants in metastasis-related genes are associated with breast cancer risk, by lymph node involvement and estrogen receptor status, in women with European and African ancestry

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