title: Comprehensive analysis of the ATM, CHEK2 and ERBB2 genes in relation to breast tumour characteristics and survival: a population-based case-control and follow-up study.
abstract: BACKGROUND
  Mutations in the ataxia-telangiectasia mutated (ATM) and checkpoint kinase 2 (CHEK2) genes and amplification of the v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2) gene have been suggested to have an important role in breast cancer aetiology. However, whether common variation in these genes has a role in the development of breast cancer or breast cancer survival in humans is still not clear.
  
  
  METHODS
  We performed a comprehensive haplotype analysis of the ATM, CHEK2 and ERBB2 genes in a Swedish population-based study, which included 1,579 breast cancer cases and 1,516 controls. We followed the cases for 8.5 years, on average, and retrieved information on the date and cause of death during that period from the nationwide Swedish causes of death registry. We selected seven haplotype-tagging SNPs (tagSNPs) in the ATM gene, six tagSNPs in the CHEK2 gene and seven tagSNPs in the ERBB2 gene that predicted both haplotypic and single locus variations in the respective genes with R2 values > or = 0.8. These tagSNPs were genotyped in the complete set of cases and controls. We computed expected haplotype dosages of the tagSNP haplotypes and included the dosages as explanatory variables in Cox proportional hazards or logistic regression models.
  
  
  RESULTS
  We found no association between any genetic variation in the ATM, CHEK2 or ERBB2 genes and breast cancer survival or the risk of developing tumours with certain characteristics.
  
  
  CONCLUSIONS
  Our results indicate that common variants in the ATM, CHEK2 or ERBB2 genes are not involved in modifying breast cancer survival or the risk of tumour-characteristic-defined breast cancer.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Nobels väg 12A, 171 77 Solna, Sweden. Kristjana.Einarsdottir@ki.se
authors.forename: Kristjana
authors.initials: K
authors.lastname: Einarsdóttir
authors.forename: Lena U
authors.initials: LU
authors.lastname: Rosenberg
authors.forename: Keith
authors.initials: K
authors.lastname: Humphreys
authors.forename: Carine
authors.initials: C
authors.lastname: Bonnard
authors.forename: Juni
authors.initials: J
authors.lastname: Palmgren
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Kee S
authors.initials: KS
authors.lastname: Chia
authors.forename: Edison T
authors.initials: ET
authors.lastname: Liu
authors.forename: Per
authors.initials: P
authors.lastname: Hall
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.forename: Sara
authors.initials: S
authors.lastname: Wedrén
mesh_terms: D000368:Aged; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D064447:Checkpoint Kinase 2; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D018734:Genes, erbB-2 / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012306:Risk; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D064447:Checkpoint Kinase 2; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases