title: Single nucleotide polymorphisms associated with risk for contralateral breast cancer in the Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study.
abstract: BACKGROUND
  Genome-wide association studies, focusing primarily on unilateral breast cancer, have identified single nucleotide polymorphisms (SNPs) in a number of genomic regions that have alleles associated with a significantly increased risk of breast cancer. In the current study we evaluate the contributions of these previously identified regions to the risk of developing contralateral breast cancer. The most strongly disease-associated SNPs from prior studies were tested for association with contralateral breast cancer. A subset of these SNPs, selected upon their main effects on contralateral breast cancer risk was further evaluated for interaction with treatment modalities and estrogen receptor (ER) status.
  
  
  METHODS
  We genotyped 21 SNPs in 708 women with contralateral breast cancer and 1394 women with unilateral breast cancer who serve as the cases and controls in the Women's Environment, Cancer and Radiation Epidemiology (WECARE) Study. Records of treatment and ER status were available for most of WECARE Study participants. Associations of SNP genotypes and risk for contralateral breast cancer were calculated with multivariable adjusted conditional logistic regression methods.
  
  
  RESULTS
  Multiple SNPs in the FGFR2 locus were significantly associated with contralateral breast cancer, including rs1219648 (per allele rate ratio (RR) = 1.25, 95%CI = 1.08-1.45). Statistically significant associations with contralateral breast cancer were also observed at rs7313833, near the PTHLH gene (per allele RR = 1.26, 95%CI = 1.08-1.47), rs13387042 (2q35) (per allele RR = 1.19, 95%CI = 1.02-1.37), rs13281615 (8q24) (per allele RR = 1.21, 95%CI = 1.04-1.40), and rs11235127 near TMEM135 (per allele RR = 1.26, 95%CI = 1.04-1.53). The A allele of rs13387042 (2q35) was significantly associated with contralateral breast cancer in ER negative first tumors while the A allele of rs11235127 (near TMEM135) was significantly associated with contralateral breast cancer in ER positive first tumors. Although some SNP genotypes appeared to modify contralateral breast cancer risk with respect to tamoxifen treatment or particular radiation doses, trend tests for such effects were not significant.
  
  
  CONCLUSIONS
  Our results indicate that some common risk variants associated with primary breast cancer also increase risk for contralateral breast cancer, and that these risks vary with the ER status of the first tumor.
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908-0717, USA. st3x@virginia.edu
authors.forename: Sharon N
authors.initials: SN
authors.lastname: Teraoka
authors.forename: Jonine L
authors.initials: JL
authors.lastname: Bernstein
authors.forename: Anne S
authors.initials: AS
authors.lastname: Reiner
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Charles F
authors.initials: CF
authors.lastname: Lynch
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Malone
authors.forename: Marilyn
authors.initials: M
authors.lastname: Stovall
authors.forename: Marinela
authors.initials: M
authors.lastname: Capanu
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liang
authors.forename: Susan A
authors.initials: SA
authors.lastname: Smith
authors.forename: Josyf
authors.initials: J
authors.lastname: Mychaleckyj
authors.forename: Xuanlin
authors.initials: X
authors.lastname: Hou
authors.forename: Lene
authors.initials: L
authors.lastname: Mellemkjaer
authors.forename: John D
authors.initials: JD
authors.lastname: Boice
authors.forename: Ashley
authors.initials: A
authors.lastname: Siniard
authors.forename: David
authors.initials: D
authors.lastname: Duggan
authors.forename: Duncan C
authors.initials: DC
authors.lastname: Thomas
authors.forename: Patrick
authors.initials: P
authors.lastname: Concannon
mesh_terms: D000483:Alleles; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000532:radiotherapy; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D012306:Risk
chemical_list: D011960:Receptors, Estrogen; D051497:Receptor, Fibroblast Growth Factor, Type 2
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