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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
Author(s) -
Roberts Michelle R.,
SuchestonCampbell Lara E.,
Zirpoli Gary R.,
Higgins Michael,
Freudenheim Jo L.,
Bandera Elisa V.,
Ambrosone Christine B.,
Yao Song
Publication year - 2017
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22565
Subject(s) - single nucleotide polymorphism , breast cancer , biology , oncology , medicine , estrogen receptor , allele , snp , cancer , genetics , genotype , gene
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. © 2016 Wiley Periodicals, Inc.