title: Nuclear receptor coregulator SNP discovery and impact on breast cancer risk.
abstract: BACKGROUND
  Coregulator proteins are "master regulators", directing transcriptional and posttranscriptional regulation of many target genes, and are critical in many normal physiological processes, but also in hormone driven diseases, such as breast cancer. Little is known on how genetic changes in these genes impact disease development and progression. Thus, we set out to identify novel single nucleotide polymorphisms (SNPs) within SRC-1 (NCoA1), SRC-3 (NCoA3, AIB1), NCoR (NCoR1), and SMRT (NCoR2), and test the most promising SNPs for associations with breast cancer risk.
  
  
  METHODS
  The identification of novel SNPs was accomplished by sequencing the coding regions of these genes in 96 apparently normal individuals (48 Caucasian Americans, 48 African Americans). To assess their association with breast cancer risk, five SNPs were genotyped in 1218 familial BRCA1/2-mutation negative breast cancer cases and 1509 controls (rs1804645, rs6094752, rs2230782, rs2076546, rs2229840).
  
  
  RESULTS
  Through our resequencing effort, we identified 74 novel SNPs (30 in NCoR, 32 in SMRT, 10 in SRC-3, and 2 in SRC-1). Of these, 8 were found with minor allele frequency (MAF) >5% illustrating the large amount of genetic diversity yet to be discovered. The previously shown protective effect of rs2230782 in SRC-3 was strengthened (OR = 0.45 [0.21-0.98], p = 0.04). No significant associations were found with the other SNPs genotyped.
  
  
  CONCLUSIONS
  This data illustrates the importance of coregulators, especially SRC-3, in breast cancer development and suggests that more focused studies, including functional analyses, should be conducted.
authors.affiliation: Program in Translational Biology & Molecular Medicine, Baylor College of Medicine, Houston, TX 77030, USA. hartmaie@bcm.edu
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Hartmaier
authors.forename: Sandrine
authors.initials: S
authors.lastname: Tchatchou
authors.forename: Alexandra S
authors.initials: AS
authors.lastname: Richter
authors.forename: Jay
authors.initials: J
authors.lastname: Wang
authors.forename: Sean E
authors.initials: SE
authors.lastname: McGuire
authors.forename: Todd C
authors.initials: TC
authors.lastname: Skaar
authors.forename: Jimmy M
authors.initials: JM
authors.lastname: Rae
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Christian
authors.initials: C
authors.lastname: Sutter
authors.forename: Nina
authors.initials: N
authors.lastname: Ditsch
authors.forename: Peter
authors.initials: P
authors.lastname: Bugert
authors.forename: Bernhard H F
authors.initials: BH
authors.lastname: Weber
authors.forename: Dieter
authors.initials: D
authors.lastname: Niederacher
authors.forename: Norbert
authors.initials: N
authors.lastname: Arnold
authors.forename: Raymonda
authors.initials: R
authors.lastname: Varon-Mateeva
authors.forename: Barbara
authors.initials: B
authors.lastname: Wappenschmidt
authors.forename: Rita K
authors.initials: RK
authors.lastname: Schmutzler
authors.forename: Alfons
authors.initials: A
authors.lastname: Meindl
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.forename: Barbara
authors.initials: B
authors.lastname: Burwinkel
authors.forename: Steffi
authors.initials: S
authors.lastname: Oesterreich
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D056918:Nuclear Receptor Coactivators / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D056918:Nuclear Receptor Coactivators