title: Circulating Adipokines and Inflammatory Markers and Postmenopausal Breast Cancer Risk.
abstract: BACKGROUND
  Adipokines and inflammation may provide a mechanistic link between obesity and postmenopausal breast cancer, yet epidemiologic data on their associations with breast cancer risk are limited.
  
  
  METHODS
  In a case-cohort analysis nested within the Women's Health Initiative Observational Study, a prospective cohort of postmenopausal women, baseline plasma samples from 875 incident breast cancer case patients and 839 subcohort participants were tested for levels of seven adipokines, namely leptin, adiponectin, resistin, interleukin-6, tumor necrosis factor-α, hepatocyte growth factor, and plasminogen activator inhibitor-1, and for C-reactive protein (CRP), an inflammatory marker. Data were analyzed by multivariable Cox modeling that included established breast cancer risk factors and previously measured estradiol and insulin levels. All statistical tests were two-sided.
  
  
  RESULTS
  The association between plasma CRP levels and breast cancer risk was dependent on hormone therapy (HT) use at baseline (P interaction = .003). In a model that controlled for multiple breast cancer risk factors including body mass index (BMI), estradiol, and insulin, CRP level was positively associated with breast cancer risk among HT nonusers (hazard ratio for high vs low CRP levels = 1.67, 95% confidence interval = 1.04 to 2.68, P trend = .029). None of the other adipokines were statistically significantly associated with breast cancer risk. Following inclusion of CRP, insulin, and estradiol in a multivariable model, the association of BMI with breast cancer was attenuated by 115%.
  
  
  CONCLUSIONS
  These data indicate that CRP is a risk factor for postmenopausal breast cancer among HT nonusers. Inflammatory mediators, together with insulin and estrogen, may play a role in the obesity-breast cancer relation.
authors.affiliation: Imperial College, London, UK (MJG); Albert Einstein College of Medicine, Bronx, NY (TW, XX, SWS, HDS, TER, RCK, DW, GYFH); University of Vermont, Burlington, VT (MC); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (JEM); Fred Hutchinson Cancer Research Center, Seattle, WA (AM); University of Texas Southwestern Medical School, Dallas, TX (PES); University of California Los Angeles, Torrence, CA (RTC); University of Iowa, Iowa City, IA (LS). m.gunter@imperial.ac.uk.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunter
authors.affiliation: Imperial College, London, UK (MJG); Albert Einstein College of Medicine, Bronx, NY (TW, XX, SWS, HDS, TER, RCK, DW, GYFH); University of Vermont, Burlington, VT (MC); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (JEM); Fred Hutchinson Cancer Research Center, Seattle, WA (AM); University of Texas Southwestern Medical School, Dallas, TX (PES); University of California Los Angeles, Torrence, CA (RTC); University of Iowa, Iowa City, IA (LS).
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Imperial College, London, UK (MJG); Albert Einstein College of Medicine, Bronx, NY (TW, XX, SWS, HDS, TER, RCK, DW, GYFH); University of Vermont, Burlington, VT (MC); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (JEM); Fred Hutchinson Cancer Research Center, Seattle, WA (AM); University of Texas Southwestern Medical School, Dallas, TX (PES); University of California Los Angeles, Torrence, CA (RTC); University of Iowa, Iowa City, IA (LS).
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.affiliation: Imperial College, London, UK (MJG); Albert Einstein College of Medicine, Bronx, NY (TW, XX, SWS, HDS, TER, RCK, DW, GYFH); University of Vermont, Burlington, VT (MC); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (JEM); Fred Hutchinson Cancer Research Center, Seattle, WA (AM); University of Texas Southwestern Medical School, Dallas, TX (PES); University of California Los Angeles, Torrence, CA (RTC); University of Iowa, Iowa City, IA (LS).
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Xue
authors.affiliation: Imperial College, London, UK (MJG); Albert Einstein College of Medicine, Bronx, NY (TW, XX, SWS, HDS, TER, RCK, DW, GYFH); University of Vermont, Burlington, VT (MC); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (JEM); Fred Hutchinson Cancer Research Center, Seattle, WA (AM); University of Texas Southwestern Medical School, Dallas, TX (PES); University of California Los Angeles, Torrence, CA (RTC); University of Iowa, Iowa City, IA (LS).
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wassertheil-Smoller
authors.affiliation: Imperial College, London, UK (MJG); Albert Einstein College of Medicine, Bronx, NY (TW, XX, SWS, HDS, TER, RCK, DW, GYFH); University of Vermont, Burlington, VT (MC); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (JEM); Fred Hutchinson Cancer Research Center, Seattle, WA (AM); University of Texas Southwestern Medical School, Dallas, TX (PES); University of California Los Angeles, Torrence, CA (RTC); University of Iowa, Iowa City, IA (LS).
authors.forename: Howard D
authors.initials: HD
authors.lastname: Strickler
authors.affiliation: Imperial College, London, UK (MJG); Albert Einstein College of Medicine, Bronx, NY (TW, XX, SWS, HDS, TER, RCK, DW, GYFH); University of Vermont, Burlington, VT (MC); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (JEM); Fred Hutchinson Cancer Research Center, Seattle, WA (AM); University of Texas Southwestern Medical School, Dallas, TX (PES); University of California Los Angeles, Torrence, CA (RTC); University of Iowa, Iowa City, IA (LS).
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Rohan
authors.affiliation: Imperial College, London, UK (MJG); Albert Einstein College of Medicine, Bronx, NY (TW, XX, SWS, HDS, TER, RCK, DW, GYFH); University of Vermont, Burlington, VT (MC); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (JEM); Fred Hutchinson Cancer Research Center, Seattle, WA (AM); University of Texas Southwestern Medical School, Dallas, TX (PES); University of California Los Angeles, Torrence, CA (RTC); University of Iowa, Iowa City, IA (LS).
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.affiliation: Imperial College, London, UK (MJG); Albert Einstein College of Medicine, Bronx, NY (TW, XX, SWS, HDS, TER, RCK, DW, GYFH); University of Vermont, Burlington, VT (MC); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (JEM); Fred Hutchinson Cancer Research Center, Seattle, WA (AM); University of Texas Southwestern Medical School, Dallas, TX (PES); University of California Los Angeles, Torrence, CA (RTC); University of Iowa, Iowa City, IA (LS).
authors.forename: Anne
authors.initials: A
authors.lastname: McTiernan
authors.affiliation: Imperial College, London, UK (MJG); Albert Einstein College of Medicine, Bronx, NY (TW, XX, SWS, HDS, TER, RCK, DW, GYFH); University of Vermont, Burlington, VT (MC); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (JEM); Fred Hutchinson Cancer Research Center, Seattle, WA (AM); University of Texas Southwestern Medical School, Dallas, TX (PES); University of California Los Angeles, Torrence, CA (RTC); University of Iowa, Iowa City, IA (LS).
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kaplan
authors.affiliation: Imperial College, London, UK (MJG); Albert Einstein College of Medicine, Bronx, NY (TW, XX, SWS, HDS, TER, RCK, DW, GYFH); University of Vermont, Burlington, VT (MC); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (JEM); Fred Hutchinson Cancer Research Center, Seattle, WA (AM); University of Texas Southwestern Medical School, Dallas, TX (PES); University of California Los Angeles, Torrence, CA (RTC); University of Iowa, Iowa City, IA (LS).
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
authors.affiliation: Imperial College, London, UK (MJG); Albert Einstein College of Medicine, Bronx, NY (TW, XX, SWS, HDS, TER, RCK, DW, GYFH); University of Vermont, Burlington, VT (MC); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (JEM); Fred Hutchinson Cancer Research Center, Seattle, WA (AM); University of Texas Southwestern Medical School, Dallas, TX (PES); University of California Los Angeles, Torrence, CA (RTC); University of Iowa, Iowa City, IA (LS).
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.affiliation: Imperial College, London, UK (MJG); Albert Einstein College of Medicine, Bronx, NY (TW, XX, SWS, HDS, TER, RCK, DW, GYFH); University of Vermont, Burlington, VT (MC); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (JEM); Fred Hutchinson Cancer Research Center, Seattle, WA (AM); University of Texas Southwestern Medical School, Dallas, TX (PES); University of California Los Angeles, Torrence, CA (RTC); University of Iowa, Iowa City, IA (LS).
authors.forename: Linda
authors.initials: L
authors.lastname: Snetselaar
authors.affiliation: Imperial College, London, UK (MJG); Albert Einstein College of Medicine, Bronx, NY (TW, XX, SWS, HDS, TER, RCK, DW, GYFH); University of Vermont, Burlington, VT (MC); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (JEM); Fred Hutchinson Cancer Research Center, Seattle, WA (AM); University of Texas Southwestern Medical School, Dallas, TX (PES); University of California Los Angeles, Torrence, CA (RTC); University of Iowa, Iowa City, IA (LS).
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Imperial College, London, UK (MJG); Albert Einstein College of Medicine, Bronx, NY (TW, XX, SWS, HDS, TER, RCK, DW, GYFH); University of Vermont, Burlington, VT (MC); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (JEM); Fred Hutchinson Cancer Research Center, Seattle, WA (AM); University of Texas Southwestern Medical School, Dallas, TX (PES); University of California Los Angeles, Torrence, CA (RTC); University of Iowa, Iowa City, IA (LS).
authors.forename: Gloria Y F
authors.initials: GY
authors.lastname: Ho
mesh_terms: D054392:Adipokines / Q000097:blood*; D052242:Adiponectin / Q000097:blood; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000097:blood* / Q000453:epidemiology* / Q000209:etiology; D002097:C-Reactive Protein / Q000378:metabolism*; D004958:Estradiol / Q000097:blood; D005260:Female; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications*; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications*; D016017:Odds Ratio; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D017698:Postmenopause; D016016:Proportional Hazards Models; D011446:Prospective Studies; D052243:Resistin / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D054392:Adipokines; D052242:Adiponectin; D014408:Biomarkers, Tumor; C066855:HGF protein, human; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D017395:Plasminogen Activator Inhibitor 1; D052243:Resistin; C051321:SERPINE1 protein, human; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D017228:Hepatocyte Growth Factor; D002097:C-Reactive Protein