title: Replication study for reported SNP associations with breast cancer survival.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Beeghly-Fadiel
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Jirong
authors.initials: J
authors.lastname: Long
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.forename: Kai
authors.initials: K
authors.lastname: Gu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.forename: Xiao Ou
authors.initials: XO
authors.lastname: Shu
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D055815:Young Adult
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8