title: Association of prolactin and its receptor gene regions with familial breast cancer.
abstract: BACKGROUND
  The contribution of prolactin (PRL) through its receptor (PRLR) to the pathogenesis and progression of human mammary tumors has received recent attention.
  
  
  OBJECTIVE
  We investigated whether genetic variation in the PRL and PRLR genes is associated with the risk of breast cancer (BC).
  
  
  METHODS
  We conducted a case-control study with a total of seven single nucleotide polymorphisms (SNPs).
  
  
  METHODS
  The study was conducted at an academic research laboratory and university clinics.
  
  
  METHODS
  A total of 441 German familial, unrelated BC cases and 552 controls matched by age, ethnicity, and geographical region participated in the study.
  
  
  METHODS
  There were no interventions.
  
  
  METHODS
  SNP genotype and haplotype distributions and haplotype interactions were correlated with the risk of BC.
  
  
  RESULTS
  Two SNPs (rs1341239 and rs12210179) within the PRL promoter regions were significantly associated with increased risk in homozygotes for the variant alleles [odds ratio (OR), 1.67 and 95% confidence interval (CI), 1.11-2.50; and OR, 2.09 and 95% CI, 1.23-3.52, respectively]. The PRL haplotype containing the variant alleles of the promoter SNPs increased significantly the risk of BC (OR 1.42, 95%CI 1.07-1.90). A PRLR haplotype was associated with a significant decrease in BC risk (OR 0.69, 95% CI 0.54-0.89). An increasing number of PRL and PRLR risk haplotypes led to a significant trend of increasing risk for BC (chi(2) = 12.15; P = 0.007).
  
  
  CONCLUSIONS
  Genetic variation in the PRL and PRLR genes was shown to influence BC risk. Additional studies are needed to further clarify the role of the PRL and PRLR genes in the risk of BC.
authors.affiliation: Division of Molecular Genetic Epidemiology C050, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. a.vaclavicek@dkfz.de
authors.forename: Annika
authors.initials: A
authors.lastname: Vaclavicek
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wagner
authors.forename: Barbara
authors.initials: B
authors.lastname: Wappenschmidt
authors.forename: Alfons
authors.initials: A
authors.lastname: Meindl
authors.forename: Rita K
authors.initials: RK
authors.lastname: Schmutzler
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Klaes
authors.forename: Michael
authors.initials: M
authors.lastname: Untch
authors.forename: Barbara
authors.initials: B
authors.lastname: Burwinkel
authors.forename: Asta
authors.initials: A
authors.lastname: Försti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011388:Prolactin / Q000235:genetics* / Q000378:metabolism; D011981:Receptors, Prolactin / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D011981:Receptors, Prolactin; D011388:Prolactin; D004247:DNA