title: Adipocytokines, inflammation, and breast cancer risk in postmenopausal women: a prospective study.
abstract: Obesity is a known risk factor for postmenopausal breast cancer; it has been postulated that adipocytokines may mediate this association. We explored the relationship between three markers altered by obesity: leptin, adiponectin, and soluble tumor necrosis factor receptor 2 (sTNF-R2), an inflammatory marker, with breast cancer risk in postmenopausal women. A nested case-control study of postmenopausal women was conducted within CLUE II, a prospective population-based cohort. Baseline plasma levels of leptin, adiponectin, and sTNF-R2 were assayed in 272 female breast cancer cases and 272 controls matched on age, date, and hour of blood draw. Conditional logistic regression was used to estimate matched odds ratios (OR) and 95% confidence intervals (CI). sTNF-R2 and leptin were independently positively associated with breast cancer risk in adjusted models. The OR for breast cancer comparing the highest to lowest tertile was 2.44 (95% CI: 1.30-4.58) for sTNF-R2 and 1.98 (95% CI: 1.20-3.29) for leptin. While higher levels of adiponectin were protective (OR for the lowest tertile = 1.63; 95% CI: 1.02-2.60), there was no dose response. A 20% reduction in the breast cancer risk associated with overweight/obesity was observed when sTNF-R2 alone was included in multivariable models. Including both sTNF-R2 and adiponectin in the models resulted in a 29% reduction in the OR. Adipocytokines and sTNF-R2 are important factors in the etiology of postmenopausal breast cancer due to adiposity. This study informs our understanding of the relationship between obesity, inflammation, and postmenopausal breast cancer and identifies potential biomarkers.
authors: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
authors: Amy L
authors: AL
authors: Gross
authors: Craig J
authors: CJ
authors: Newschaffer
authors: Judith
authors: J
authors: Hoffman-Bolton
authors: Nader
authors: N
authors: Rifai
authors: Kala
authors: K
authors: Visvanathan
mesh_terms: D054392:Adipokines / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D020738:Leptin / Q000097:blood; D008875:Middle Aged; D009570:Nitriles / Q000097:blood; D009765:Obesity / Q000097:blood; D017698:Postmenopause / Q000097:blood*; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D054392:Adipokines; D020738:Leptin; D009570:Nitriles; C036546:adiponitrile
references: J Natl Cancer Inst. 1998 Apr 1;90(7):512-8
references: 9539246
references: J Clin Endocrinol Metab. 2007 Apr;92(4):1510-6
references: 17213279
references: Cancer Epidemiol Biomarkers Prev. 2005 Oct;14(10):2413-8
references: 16214925
references: J Clin Endocrinol Metab. 2001 May;86(5):1930-5
references: 11344187
references: J Clin Endocrinol Metab. 2004 Mar;89(3):1102-7
references: 15001594
references: Cancer Causes Control. 2000 May;11(5):383-8
references: 10877331
references: Clin Cancer Res. 2003 Nov 15;9(15):5699-704
references: 14654554
references: Cancer Epidemiol Biomarkers Prev. 2011 Apr;20(4):665-71
references: 21307303
references: Br J Cancer. 2009 Feb 24;100(4):578-82
references: 19223908
references: Int J Cancer. 1999 Feb 9;80(4):523-6
references: 9935151
references: Cytokine. 2011 Nov;56(2):338-42
references: 21802312
references: Trends Endocrinol Metab. 2012 Feb;23(2):83-9
references: 22169755
references: Cancer Epidemiol Biomarkers Prev. 2003 Sep;12(9):945-6
references: 14504210
references: Immunol Lett. 1994 Jul;41(2-3):229-34
references: 8002043
references: Eur J Haematol. 1995 Jan;54(1):1-8
references: 7859870
references: Nat Rev Cancer. 2004 Aug;4(8):579-91
references: 15286738
references: J Natl Cancer Inst. 2003 Aug 20;95(16):1218-26
references: 12928347
references: Int J Behav Med. 2011 Dec;18(4):333-41
references: 21336679
references: J Leukoc Biol. 2010 Jul;88(1):33-9
references: 20360405
references: Eur J Endocrinol. 2000 Jul;143(1):55-60
references: 10870031
references: Obesity (Silver Spring). 2011 Jul;19(7):1482-91
references: 21233809
references: Cytokine Growth Factor Rev. 1996 Oct;7(3):231-40
references: 8971478
references: Breast Cancer Res Treat. 2004 Aug;86(3):191-6
references: 15567935
references: Endocr Relat Cancer. 2007 Sep;14(3):669-77
references: 17914097
references: Nat Rev Cancer. 2011 Nov 24;11(12):886-95
references: 22113164
references: JAMA. 1997 Nov 5;278(17):1407-11
references: 9355998
references: Cancer Prev Res (Phila). 2011 Sep;4(9):1449-56
references: 21680707