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
Published Date:Sep 21 2016
Source:Mol Carcinog. 56(3):1000-1009.
Pubmed Central ID:PMC5310990
Funding:U58 DP003931/DP/NCCDPHP CDC HHS/United States
R25 CA113951/CA/NCI NIH HHS/United States
P30 CA072720/CA/NCI NIH HHS/United States
P01 CA151135/CA/NCI NIH HHS/United States
T32 CA009001/CA/NCI NIH HHS/United States
R01 CA100598/CA/NCI NIH HHS/United States
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.
2,671 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.
Supporting Files:No Additional Files
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