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 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. © 2016 Wiley Periodicals, Inc.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 21, 2016
- Source ID
- 10.1002/mc.22565
Entities
People
- Christine B. Ambrosone
- Elisa V. Bandera
- Gary R. Zirpoli
- Jo L Freudenheim
- Lara E. Sucheston‐campbell
- Michael Higgins
- Michelle R. Roberts
- Song Yao
Organizations
- Centers for Disease Control and Prevention
- Harvard Medical School
- National Cancer Institute
- National Institutes of Health
- Ohio State University
- Roswell Park Comprehensive Cancer Center
- Rutgers University–New Brunswick
- The Breast Cancer Research Foundation
- United States Department of Defense
- University at Buffalo