title: Do adipokines underlie the association between known risk factors and breast cancer among a cohort of United States women?
abstract: BACKGROUND
  Obesity is a well-established risk factor for postmenopausal breast cancer, but mechanisms underlying the association are unclear. Adipocyte-derived, cytokine-like adipokines have been suggested as contributory factors. To evaluate their association with breast cancer risk factors and breast cancer risk, we conducted a nested case-control study of 234 postmenopausal breast cancer cases and 234 controls in a cohort of U.S. women with prospectively-collected serum samples obtained in the mid 1970s and followed for up to 25 years.
  
  
  METHODS
  Adiponectin, absolute plasminogen activator inhibitor-1 (aPAI-1), and resistin were measured by a multiplex immunoassay. Sex hormones were available for 67 cases and 67 controls.
  
  
  RESULTS
  Among controls, we found that lower levels of adiponectin and higher levels of aPAI-1 were correlated with increasing levels of estradiol (Spearman r=-0.26, p-value=0.033; r=0.42, p=0.0003), decreasing levels of sex hormone binding globulin (r=0.38, p=0.0013; r=-0.32, p=0.0076), and increasing body mass index (BMI) (r=-0.31, p=<0.0001; r=0.39, p=<0.0001). Hormones were not associated with resistin. Among the relatively small percentage of women using postmenopausal hormones at the time of blood collection (13.7%), aPAI-1 levels were higher than in non-users (p=0.0054). Breast cancer risk was not associated with circulating levels of adiponectin (age-adjusted p for linear trend=0.43), aPAI-1 (p=0.78), or resistin (p=0.91). The association was not confounded by BMI, parity, age at first full-term birth, age at menopause, current postmenopausal hormone use, and circulating sex steroid hormones. Furthermore, adipokine associations were not modified by BMI (p>0.05). The lack of association with risk may be due to measurement error of the laboratory assays.
  
  
  CONCLUSIONS
  lower levels of adiponectin and higher levels of aPAI-1 measured in prospectively-collected serum from postmenopausal women were associated with increasing BMI but not breast cancer risk.
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA. mia.gaudet@einstein.yu.edu
authors.forename: Mia M
authors.initials: MM
authors.lastname: Gaudet
authors.forename: Roni T
authors.initials: RT
authors.lastname: Falk
authors.forename: Gretchen L
authors.initials: GL
authors.lastname: Gierach
authors.forename: James V
authors.initials: JV
authors.lastname: Lacey
authors.forename: Barry I
authors.initials: BI
authors.lastname: Graubard
authors.forename: Joanne F
authors.initials: JF
authors.lastname: Dorgan
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
mesh_terms: D054392:Adipokines / Q000097:blood*; D052242:Adiponectin / Q000097:blood; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000097:blood* / Q000453:epidemiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D010865:Pilot Projects; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D015203:Reproducibility of Results; D052243:Resistin / Q000097:blood; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D014481:United States / Q000453:epidemiology
chemical_list: D054392:Adipokines; D052242:Adiponectin; D017395:Plasminogen Activator Inhibitor 1; C499624:RETN protein, human; D052243:Resistin; D012738:Sex Hormone-Binding Globulin; D004958:Estradiol