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

详细信息    查看全文

• 作者：Michelle R. Roberts ; Lara E. Sucheston-Campbell ; Gary R. Zirpoli ; Michael Higgins ; Jo L. Freudenheim ; Elisa V. Bandera ; Christine B. Ambrosone and Song Yao
• 刊名：Molecular Carcinogenesis
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：56
• 期：3
• 页码：1000-1009
• 全文大小：222K
• ISSN：1098-2744

文摘

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.