title: Common ERBB2 polymorphisms and risk of breast cancer in a white British population: a case-control study.
abstract: BACKGROUND
  About two-thirds of the excess familial risk associated with breast cancer is still unaccounted for and may be explained by multiple weakly predisposing alleles. A gene thought to be involved in low-level predisposition to the disease is ERBB2 (HER2). This gene is involved in cell division, differentiation, and apoptosis and is frequently amplified in breast tumours. Its amplification correlates with poor prognosis. Moreover, the coding polymorphism I655V has previously been associated with an increased risk of breast cancer.
  
  
  METHODS
  We aimed to determine if common polymorphisms (frequency >or= 5%) in ERBB2 were associated with breast cancer risk in a white British population. Five single-nucleotide polymorphisms (SNPs) were selected for study: SNP 1 near the promoter, SNP 2 in intron 1, SNP 3 in intron 4, SNP 4 in exon 17 (I655V), and SNP 5 in exon 27 (A1170P). We tested their association with breast cancer in a large case-control study (n = 2192 cases and 2257 controls).
  
  
  RESULTS
  There were no differences in genotype frequencies between cases and controls for any of the SNPs examined. To investigate the possibility that a common polymorphism not included in our study might be involved in breast cancer predisposition, we also constructed multilocus haplotypes. Our set of SNPs generated all existing (n = 6) common haplotypes and no differences were seen in haplotype frequencies between cases and controls (P = 0.44).
  
  
  CONCLUSIONS
  In our population, common ERBB2 polymorphisms are not involved in predisposition to breast cancer.
authors.affiliation: Department of Oncology, University of Cambridge, Strangeways Research Laboratories, Cambridge, UK. patrick@srl.cam.ac.uk
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Benusiglio
authors.forename: Fabienne
authors.initials: F
authors.lastname: Lesueur
authors.forename: Craig
authors.initials: C
authors.lastname: Luccarini
authors.forename: Donald M
authors.initials: DM
authors.lastname: Conroy
authors.forename: Mitul
authors.initials: M
authors.lastname: Shah
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Nick E
authors.initials: NE
authors.lastname: Day
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Paul D
authors.initials: PD
authors.lastname: Pharoah
authors.forename: Bruce Aj
authors.initials: BA
authors.lastname: Ponder
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004739:England; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007438:Introns; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000502:physiology; D012307:Risk Factors; D044465:White People / Q000235:genetics*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases
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