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
N1 - Funding Information:
This work was supported in part by grants from the US National Institutes of Health (R01 CA100598, P01CA151135, and P30CA072720), US Army Medical Research and Material Command (DAMD-17-01-1-0334), the Breast Cancer Research Foundation, and a gift from the Philip L. Hubbell family. MRR was supported by DAMD W81XWH-11-1-0024, a predoctoral fellowship from the Department of Defense Breast Cancer Research Program, R25-CA11395102, an NCI predoctoral award, and T32-CA009001, an NIH National Research Service Award. The New Jersey State Cancer Registry is supported by the National Program of Cancer Registries of the Centers for Disease Control and Prevention under cooperative agreement 1US58DP003931-01 awarded to the New Jersey Department of Health. The collection of New Jersey cancer incidence data is also supported by the Surveillance, Epidemiology, and End Results program of the National Cancer Institute under contract N01-PC-2010-0027 and the State of New Jersey. The funding agents played no role in the design, collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication.
Publisher Copyright:
© 2016 Wiley Periodicals, Inc.
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
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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 -