Replication study for reported SNP associations with breast cancer survival.

Beeghly-Fadiel A, Zheng W, Lu W, Long J, Zheng Y, Cai H, Gu K, Chen Z, Cai Q, Gao YT, Shu XO
J Cancer Res Clin Oncol. 2012 138 (6): 1019-26

PMID: 22367361 · PMCID: PMC3810152 · DOI:10.1007/s00432-012-1174-6

PURPOSE - Nine previously reported associations between single nucleotide polymorphisms (SNPs) and breast cancer outcomes from the Shanghai Breast Cancer Study (Stage 1) were further evaluated in relation to disease-free survival (DFS) and overall survival (OS) among 5,192 additional breast cancer patients (Stage 2).

METHODS - Hazard ratios (HR) and 95% confidence intervals (CI) were calculated by proportional hazards regression in models adjusted for age, disease stage, estrogen and progesterone receptor status, and treatment regimens.

RESULTS - Two SNPs had generally consistent results and significant associations with OS in combined analyses. Compared to women with MMP7 rs11225297 AA genotypes, OS was moderately better for women with AT genotypes (HR: 0.8, 95% CI: 0.7-1.0) and much better for women with TT genotypes (HR: 0.4, 95% CI: 0.2-0.8). Compared to women with MMP8 rs11225395 CC genotypes, OS was slightly better for women with CT genotypes (HR: 0.9, 95% CI: 0.7-1.1) and moderately better for women with TT genotypes (HR: 0.6, 95% CI: 0.4-0.9). Joint analysis showed significant dose-response relationships with increasing numbers of rare alleles for both OS (p < 0.001) and DFS (p = 0.001).

CONCLUSIONS - A functional variant in MMP8 and a SNP in high linkage disequilibrium with a functional variant in MMP7 were significantly associated with breast cancer survival in a large two-stage survival study among Chinese women. This supports the hypothesis that SNPs in matrix metalloproteinase genes may influence breast cancer prognosis; additional research on these and other SNPs in genes important in metastasis, angiogenesis, and the regulation of the tumor microenvironment is warranted.

MeSH Terms (23)

Adult Aged Alleles Breast Neoplasms Case-Control Studies China Cohort Studies Disease-Free Survival Female Follow-Up Studies Genotype Humans Linkage Disequilibrium Matrix Metalloproteinase 7 Matrix Metalloproteinase 8 Middle Aged Neoplasm Staging Polymorphism, Single Nucleotide Prognosis Prospective Studies Receptors, Estrogen Receptors, Progesterone Young Adult

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