title: Metabolic syndrome biomarkers and early breast cancer in Saudi women: evidence for the presence of a systemic stress response and/or a pre-existing metabolic syndrome-related neoplasia risk?
abstract: BACKGROUND
  Obesity has been linked to many adverse health consequences, including breast cancer. This study aims to determine adipocytokine and other biological changes in recently diagnosed breast cancer patients before therapy is started.
  
  
  METHODS
  A total of 109 female Saudi subjects [56 newly diagnosed, treatment-naïve, histologically-confirmed breast cancer cases and 53 age- and BMI-matched controls] were enrolled in this study. Anthropometric data were collected. Serum insulin, adipocytokines and plasminogen activator inhibitor-1 (PAI-1) concentrations were measured using a customized multiplex Luminex assay. Hypersensitive C-Reactive Protein (CRP), tumor necrosis factor-alpha (TNF-α), and angiotensin II (ANG II) were measured using ELISA.
  
  
  RESULTS
  A few days in the diagnosis, breast cancer subjects had significantly higher systolic blood pressure (p = 0.03), glucose (p = 0.01), triglycerides (p = 0.001), leptin (p = 0.044), resistin (p = 0.04), ANG II (p = 0.02), TNF-α (p = 0.045), and CRP (p = 0.04) than the controls. On the other hand, HDL (p = 0.01) and adiponectin (p = 0.02) were significantly lower in cancer subjects than controls. A significant association was found between elevated triglycerides (TG) and breast cancer [OR (95% CI), 6.1(1.8, 15.6), p = 0.004], as well as elevated ANG II [OR (95% CI), 5.2(1.2, 14.3), p = 0.03]. On the other hand, aPAI and HDL correlated negatively with breast cancer [OR (95% CI), 0.076(0.01, 0.34), p = 0.001; 0.30(0.09, 0.95), p 0.04, respectively].
  
  
  CONCLUSIONS
  Circulating ANGII and triglycerides were positively associated with early breast cancer. In contrast, HDL-cholesterol correlated negatively with ANG II and aPAI in these patients. This suggests that patients with recently diagnosed breast cancer have biochemical changes consistent with an activated stress response and/or that patients with metabolic syndrome manifestations have a higher risk of developing this disease.
authors: Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia (KSA).
authors: Majed S
authors: MS
authors: Alokail
authors: Nasser
authors: N
authors: Al-Daghri
authors: Amal
authors: A
authors: Abdulkareem
authors: Hossam M
authors: HM
authors: Draz
authors: Sobhy M
authors: SM
authors: Yakout
authors: Abdullah M
authors: AM
authors: Alnaami
authors: Shaun
authors: S
authors: Sabico
authors: Amal M
authors: AM
authors: Alenad
authors: George P
authors: GP
authors: Chrousos
mesh_terms: D054392:Adipokines / Q000097:blood; D000328:Adult; D000804:Angiotensin II / Q000097:blood; D018912:Arabs; D014408:Biomarkers, Tumor / Q000097:blood*; D001794:Blood Pressure; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis / Q000208:ethnology* / Q000503:physiopathology; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D003430:Cross-Sectional Studies; D055088:Early Detection of Cancer; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D016015:Logistic Models; D024821:Metabolic Syndrome / Q000097:blood / Q000175:diagnosis / Q000208:ethnology* / Q000503:physiopathology; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000097:blood / Q000175:diagnosis / Q000208:ethnology* / Q000503:physiopathology; D016017:Odds Ratio; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D012529:Saudi Arabia / Q000453:epidemiology; D013312:Stress, Physiological; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D054392:Adipokines; D014408:Biomarkers, Tumor; D008076:Cholesterol, HDL; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D002097:C-Reactive Protein
references: Int J Cancer. 2007 Aug 15;121(4):856-62
references: 17397032
references: J Am Coll Cardiol. 2010 Jun 22;55(25):2846-54
references: 20579542
references: Arch Intern Med. 2006 Nov 27;166(21):2395-402
references: 17130395
references: Ann Epidemiol. 2008 Sep;18(9):671-7
references: 18794007
references: Obes Rev. 2009 Nov;10(6):660-70
references: 19460113
references: Metabolism. 2006 Dec;55(12):1630-6
references: 17142136
references: Endocrine. 2005 Feb;26(1):19-24
references: 15805581
references: Cancer Epidemiol Biomarkers Prev. 2005 Oct;14(10):2413-8
references: 16214925
references: Mol Cell Endocrinol. 2013 Sep 25;378(1-2):59-69
references: 22684034
references: Nat Rev Endocrinol. 2009 Jul;5(7):374-81
references: 19488073
references: N Engl J Med. 2003 Apr 24;348(17):1625-38
references: 12711737
references: Acta Diabetol. 2002 Sep;39(3):105-10
references: 12357293
references: Endocr Dev. 2010;19:45-52
references: 20551667
references: PLoS One. 2012;7(4):e35667
references: 22536420
references: Hypertension. 1999 Aug;34(2):320-5
references: 10454461
references: J Hypertens. 2000 Mar;18(3):249-54
references: 10726709
references: Physiol Res. 2004;53(2):123-9
references: 15046547
references: J Natl Cancer Inst. 2004 Aug 4;96(15):1152-60
references: 15292387
references: Eur J Surg Oncol. 1995 Oct;21(5):504-9
references: 7589594
references: Cardiovasc Diabetol. 2009 Jun 23;8:33
references: 19545451
references: Maturitas. 2008 May 20;60(1):19-30
references: 18485631
references: J Clin Endocrinol Metab. 2007 Mar;92(3):1041-8
references: 17192291
references: J Natl Cancer Inst. 2009 Jan 7;101(1):48-60
references: 19116382
references: Kidney Int. 2011 Jan;79(2):162-8
references: 20944545
references: J Clin Endocrinol Metab. 2007 Apr;92(4):1510-6
references: 17213279
references: Am J Clin Nutr. 2007 Sep;86(3):s823-35
references: 18265476
references: Anticancer Res. 1999 Mar-Apr;19(2B):1427-32
references: 10365118
references: Breast Cancer Res. 2011 Mar 30;13(2):R34
references: 21450081
references: Cancer Epidemiol Biomarkers Prev. 2002 Nov;11(11):1361-8
references: 12433712
references: J Am Geriatr Soc. 2006 Jan;54(1):63-9
references: 16420199
references: Cancer. 2001 Aug 15;92(4):720-9
references: 11550140
references: Diabetes Res Clin Pract. 2006 Jun;72(3):244-50
references: 16377022
references: Anticancer Res. 2006 Jan-Feb;26(1A):167-73
references: 16475694
references: Menopause. 2011 Nov;18(11):1198-204
references: 21712732
references: Nat Rev Cancer. 2010 Nov;10(11):745-59
references: 20966920
references: Arch Physiol Biochem. 2008 Feb;114(1):63-70
references: 18465360
references: Trends Endocrinol Metab. 2005 Sep;16(7):293-9
references: 16061390
references: Obes Rev. 2006 Nov;7(4):333-40
references: 17038127
references: Cytokine. 2004 Jul 21-Aug 7;27(2-3):58-65
references: 15242694
references: Nutr Metab Cardiovasc Dis. 2010 Jan;20(1):41-8
references: 19361966
references: Diabetologia. 2006 May;49(5):945-52
references: 16557372
references: Cancer Epidemiol Biomarkers Prev. 2012 Aug;21(8):1381-4
references: 22593241