title: Amphiregulin as a Novel Serum Marker of Puberty in Girls.
abstract: OBJECTIVE
  Amphiregulin is a member of the epidermal growth factor family. In breast tissue, amphiregulin is a mediator of estrogen and progesterone signaling. The objectives were to examine the relationship of amphiregulin levels during peripuberty with estrogen levels. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: The participants in this analysis were a subset from a longitudinal study of pubertal maturation, the Breast Cancer and the Environment Research Program. They were recruited between ages 3 and 7 years. Blood specimens were selected for hormone analysis between 24 months before and 6 months after breast development. Serum amphiregulin levels were analyzed using enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Amphiregulin levels were measured in 188 girls; 8.5% had a maternal history of breast cancer, and 30.9% of samples were below the limit of detection. Amphiregulin levels were greatest at 18 months before the onset of breast development (P < .006), and the rise in estrone levels between -24 and -18 months was correlated with the increase in amphiregulin levels in the same time period (P = .0002). After adjustment for time relative to breast development, amphiregulin levels were associated with maternal breast cancer (P = .024). Tracking of amphiregulin levels was highly significant (P < .0001) within a given individual.
  
  
  CONCLUSIONS
  Amphiregulin levels peaked at 18 months before the onset of breast development, were temporally related to the rise in serum estrone, and were significantly associated with maternal history of breast cancer. Elevated amphiregulin levels at puberty might be a predictor of increased breast cancer risk.
authors.affiliation: Division of Adolescent and Transition Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio. Electronic address: frank.biro@cchmc.org.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Biro
authors.affiliation: Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Pinney
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Schwartz
authors.affiliation: Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Department of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Cattran
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, Michigan.
authors.forename: Sandra Z
authors.initials: SZ
authors.lastname: Haslam
mesh_terms: D066258:Amphiregulin / Q000097:blood*; D015415:Biomarkers / Q000032:analysis; D001940:Breast / Q000254:growth & development; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D004967:Estrogens / Q000097:blood*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D011627:Puberty / Q000097:blood*; D012741:Sexual Maturation / Q000502:physiology*
chemical_list: D066258:Amphiregulin; D015415:Biomarkers; D004967:Estrogens
keywords: Amphiregulin; Breast cancer; Puberty