title: No association between genetic variants in angiogenesis and inflammation pathway genes and breast cancer survival among Chinese women.
abstract: BACKGROUND
  Angiogenesis and inflammation are implicated in breast cancer prognosis; however, the role of individual germline variation in related genes is unknown.
  
  
  METHODS
  A two-stage candidate pathway association study was conducted among 6983 Chinese women. Stage 1 included 2884 women followed for a median of 5.7 years; Stage 2 included 4099 women followed for a median of 4.0 years. Cox proportional hazards regression was used to estimate the effects of genetic variants on disease-free survival (DFS) and overall survival (OS).
  
  
  RESULTS
  Stage 1 included genotyping of 506 variants in 22 genes; analysis was conducted for 370 common variants. Nominally significant associations with DFS and/or OS were found for 20 loci in ten genes in Stage 1; variants in 19 loci were successfully genotyped and evaluated in Stage 2. In analyses of both study stages combined, nominally significant associations were found for nine variants in seven genes; none of these associations surpassed a significance threshold level corrected for the total number of variants evaluated in this study.
  
  
  CONCLUSIONS
  No association with survival was found for 370 common variants in 22 angiogenesis and inflammation pathway genes among Chinese women with breast cancer.
  
  
  CONCLUSIONS
  Our data do not support a large role for common genetic variation in 22 genes in breast cancer prognosis; research on angiogenesis and inflammation genes should focus on common variation in other genes, rare host variants, or tumor alterations.
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Tsogzolmaa
authors.initials: T
authors.lastname: Dorjgochoo
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Ma
authors.forename: Jirong
authors.initials: J
authors.lastname: Long
authors.forename: Pingping
authors.initials: P
authors.lastname: Bao
authors.forename: Ben
authors.initials: B
authors.lastname: Zhang
authors.forename: Wanqing
authors.initials: W
authors.lastname: Wen
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Xiao Ou
authors.initials: XO
authors.lastname: Shu
authors.forename: Alicia
authors.initials: A
authors.lastname: Beeghly-Fadiel
mesh_terms: D001943:Breast Neoplasms / Q000098:blood supply* / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D002681:China / Q000453:epidemiology; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000453:epidemiology / Q000235:genetics*; D058922:Inflammatory Breast Neoplasms / Q000098:blood supply / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000453:epidemiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
keywords: Angiogenesis genes; Breast cancer survival; CCL2; CCL5; CCR2; COL18A1; Chinese women; DFS; DNA; ER; FGFR4; FLT1; Genetic variants; HER2; HIF1A; HPGD; IL10; IL1B; IL6; Inflammation pathway genes; KDR; MAF; MMP1; MMP13; MMP2; MMP3; MMP7; MMP9; OS; PLAU; POSTN; PR; PTGES; PTGIS; PTGS2; SBCS; SBCSS; SERPINE1; SWHS; Shanghai Breast Cancer Study; Shanghai Breast Cancer Survival Study; Shanghai Women's Health Study; TGFB1; THBS1; VEGFA; chemokine (C-C motif) ligand 2; chemokine (C-C motif) ligand 5; chemokine (C-C motif) receptor 2; collagen, type XVIII, alpha 1; deoxyribonucleic acid; disease-free survival; estrogen receptor; fibroblast growth factor receptor 4; fms-related tyrosine kinase 1; human epidermal growth factor receptor 2; hydroxyprostaglandin dehydrogenase; hypoxia inducible factor 1, alpha subunit; interleukin 1, beta; interleukin 10; interleukin 6; kb; kilobase; kinase insert domain receptor; matrix metallopeptidase 1; matrix metallopeptidase 13; matrix metallopeptidase 2; matrix metallopeptidase 3; matrix metallopeptidase 7; matrix metallopeptidase 9; minor allele frequency; overall survival; periostin, osteoblast specific factor; plasminogen activator, urokinase; progesterone receptor; prostaglandin E synthase; prostaglandin I2 synthase; prostaglandin-endoperoxide synthase 2; serpin peptidase inhibitor, clade E, member 1 (previously known as PAI1); thrombospondin 1; transforming growth factor, beta 1; vascular endothelial growth factor A