title: Genetic variation in PRL and PRLR, and relationships with serum prolactin levels and breast cancer risk: results from a population-based case-control study in Poland.
abstract: BACKGROUND
  Studies suggest that high circulating levels of prolactin increase breast cancer risk. It is unclear if genetic variations in prolactin (PRL) or prolactin receptor (PRLR) genes also play a role. Thus, we examined the relationship between single nucleotide polymorphisms (SNPs) in PRL and PRLR, serum prolactin levels and breast cancer risk in a population-based case-control study.
  
  
  METHODS
  We genotyped 8 PRL and 20 PRLR tag SNPs in 1965 breast cancer cases and 2229 matched controls, aged 20-74, and living in Warsaw or Łódź, Poland. Serum prolactin levels were measured by immunoassay in a subset of 773 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for genotype associations with breast cancer risk were estimated using unconditional logistic regression, adjusted for age and study site. Geometric mean prolactin levels were estimated using linear regression models adjusted for age, study site, blood collection time, and menstrual cycle day (premenopausal women).
  
  
  RESULTS
  Three SNPs were associated with breast cancer risk: in premenopausal women, PRLR rs249537 (T vs. C per-allele OR 1.39, 95% CI 1.07 - 1.80, P = 0.01); and in postmenopausal women, PRLR rs7718468 (C vs. T per-allele OR 1.16, 95% CI 1.03 - 1.30, P = 0.01) and PRLR rs13436213 (A vs. G per-allele OR 1.13 95% CI 1.01 - 1.26, P = 0.04). However, mean serum prolactin levels for these SNPs did not vary by genotype (P-trend > 0.05). Other SNPs were associated with serum prolactin levels: PRLR rs62355518 (P-trend = 0.01), PRLR rs10941235 (P-trend = 0.01), PRLR rs1610218 (P-trend = 0.01), PRLR rs34024951 (P-trend = 0.02), and PRLR rs9292575 (P-trend = 0.03) in premenopausal controls and PRL rs849872 (P-trend = 0.01) in postmenopausal controls.
  
  
  CONCLUSIONS
  Our data provide limited support for an association between common variations in PRLR and breast cancer risk. Altered serum prolactin levels were not associated with breast cancer risk-associated variants, suggesting that common genetic variation is not a strong predictor of prolactin-associated breast cancer risk in this population.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Rockville, MD 20852, USA. sarah.nyante@nih.gov
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Nyante
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Faupel-Badger
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.forename: Mia M
authors.initials: MM
authors.lastname: Gaudet
authors.forename: Roni T
authors.initials: RT
authors.lastname: Falk
authors.forename: Abegail A
authors.initials: AA
authors.lastname: Andaya
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.forename: Beata
authors.initials: B
authors.lastname: Peplonska
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Vonderhaar
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Closas
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000235:genetics; D017697:Premenopause / Q000235:genetics; D011388:Prolactin / Q000097:blood* / Q000235:genetics*; D011981:Receptors, Prolactin / Q000235:genetics*; D012307:Risk Factors
chemical_list: D011981:Receptors, Prolactin; D011388:Prolactin