title: Genetic variation in the chromosome 17q23 amplicon and breast cancer risk.
abstract: BACKGROUND
  Gene amplification leading to overexpression is a common event in breast tumors that is linked to tumor development and progression. The 17q23 region is amplified in >40% of breast tumors and contains several candidate oncogenes. Because common genetic variation in several oncogenes has been associated with cancer risk, we assessed the relevance of common variants in the 17q23 candidate oncogenes to breast cancer.
  
  
  METHODS
  We investigated 60 polymorphisms in the TUBD1, SEPT4, PRKCA, TBX2, TBX4, TEX14, TLK2, YPEL2, and PPM1E genes from this amplicon for association with breast cancer risk among 798 Caucasian breast cancer cases and 843 unaffected Caucasian controls from the Mayo Clinic.
  
  
  RESULTS
  Eight polymorphisms in PRKCA, TBX4, TLK2, and YPEL2 displayed significant dose-response associations with breast cancer risk (P(trend) < 0.05). Of these, PRKCA rs7342847 and TLK2 rs2245092 and rs733025 were also associated with hormone receptor-positive breast cancer: PRKCA rs7342847 (odds ratio, 0.7; 95% confidence interval, 0.6-0.9; P(trend) = 0.002) and TLK2 rs733025 and rs2245092 (both: odds ratio, 0.8; 95% confidence interval, 0.7-1.0; P(trend) = 0.03). Interactions between SEPT4 rs758377 and TEX14 rs302864 (P(interaction) = 0.0003) and between TLK2 rs733025 and YPEL2 rs16943468 (P(interaction) = 0.05) for risk of breast cancer were also observed.
  
  
  CONCLUSIONS
  These findings suggest that single polymorphisms and combinations of polymorphisms within candidate oncogenes from the 17q23 amplicon may influence risk of breast cancer overall and possibly specific molecular subtypes of breast tumors. The findings are discussed within the context of the results from two independent data sets.
authors.affiliation: Division of Population Health, Alberta Cancer Board, Calgary, Alberta, Canada.
authors.forename: Linda E
authors.initials: LE
authors.lastname: Kelemen
authors.forename: Xianshu
authors.initials: X
authors.lastname: Wang
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Fredericksen
authors.forename: V Shane
authors.initials: VS
authors.lastname: Pankratz
authors.forename: Paul D P
authors.initials: PD
authors.lastname: Pharoah
authors.forename: Shahana
authors.initials: S
authors.lastname: Ahmed
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Goode
authors.forename: Janet E
authors.initials: JE
authors.lastname: Olson
authors.forename: Fergus J
authors.initials: FJ
authors.lastname: Couch
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors