title: ESR1 and EGF genetic variation in relation to breast cancer risk and survival.
abstract: BACKGROUND
  Oestrogen exposure is a central factor in the development of breast cancer. Oestrogen receptor alpha (ESR1) is the main mediator of oestrogen effect in breast epithelia and has also been shown to be activated by epidermal growth factor (EGF). We sought to determine if common genetic variation in the ESR1 and EGF genes affects breast cancer risk, tumour characteristics or breast cancer survival.
  
  
  METHODS
  We genotyped 157 single nucleotide polymorphisms (SNPs) in ESR1 and 54 SNPs in EGF in 92 Swedish controls and selected haplotype tagging SNPs (tagSNPs) that could predict both single SNP and haplotype variation in the genes with an R2 of at least 0.8. The tagSNPs were genotyped in 1,590 breast cancer cases and 1,518 controls, and their association with breast cancer risk, tumour characteristics and survival were assessed using unconditional logistic regression models, Cox proportional hazard models and haplotype analysis.
  
  
  RESULTS
  The single tagSNP analysis did not reveal association evidence for breast cancer risk, tumour characteristics, or survival. A multi-locus analysis of five adjacent tagSNPs suggested a region in ESR1 (between rs3003925 and rs2144025) for association with breast cancer risk (p = 0.001), but the result did not withstand adjustment for multiple comparisons (p = 0.086). A similar region was also implicated by haplotype analyses, but its significance needs to be verified by follow-up analysis.
  
  
  CONCLUSIONS
  Our results do not support a strong association between common variants in the ESR1 and EGF genes and breast cancer risk, tumour characteristics or survival.
authors.affiliation: Centre for Health Services Research, School of Population Health, University of Western Australia, 6009 Crawley, Perth, Western Australia.
authors.forename: Kristjana
authors.initials: K
authors.lastname: Einarsdóttir
authors.forename: Hatef
authors.initials: H
authors.lastname: Darabi
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Yen Ling
authors.initials: YL
authors.lastname: Low
authors.forename: Yu Qing
authors.initials: YQ
authors.lastname: Li
authors.forename: Carine
authors.initials: C
authors.lastname: Bonnard
authors.forename: Arvid
authors.initials: A
authors.lastname: Sjölander
authors.forename: Kamila
authors.initials: K
authors.lastname: Czene
authors.forename: Sara
authors.initials: S
authors.lastname: Wedrén
authors.forename: Edison T
authors.initials: ET
authors.lastname: Liu
authors.forename: Per
authors.initials: P
authors.lastname: Hall
authors.forename: Keith
authors.initials: K
authors.lastname: Humphreys
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004815:Epidermal Growth Factor / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016019:Survival Analysis; D013548:Sweden / Q000453:epidemiology
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004815:Epidermal Growth Factor