title: Inflammatory biomarkers, aspirin, and risk of colorectal cancer: Findings from the physicians' health study.
abstract: Chronic inflammation has been implicated in colorectal carcinogenesis. However, the associations between plasma inflammatory markers and risk of colorectal cancer have been inconsistent.
  
  
  
  In a nested case-control study in the Physicians' Health Study, we prospectively investigated the associations of plasma C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor receptor 2 (TNFR-2) with risk of colorectal cancer, and whether aspirin modified these associations among 268 colorectal cancer patients and 446 age- and smoking-matched controls.
  
  
  
  In multivariate-adjusted models, plasma levels of CRP, IL-6 and TNFR-2 were not significantly associated with risk of colorectal cancer, although a positive trend was observed for TNFR-2 (RRhighestvs.lowestquartile=1.55; 95% CI=0.95-2.54; Ptrend=0.05). We observed a statistically significant association between elevated TNFR-2 levels and colorectal cancer risk in the placebo arm (RRhighestvs.lowesttertile=1.77; 95% CI=1.02-3.06; Ptrend=0.02), but not in the aspirin arm (Ptrend=0.72). However, the interaction between TNFR-2 and aspirin was not statistically significant (Pinteraction=0.34).
  
  
  
  Plasma inflammatory markers were not significantly associated with colorectal cancer risk among men, though there was a statistically non-significant positive trend between TNFR-2 and colorectal cancer risk. More studies are required to understand the relationship between the role of TNFα pathway, aspirin, and colorectal cancer risk.
authors: Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, United States; Medical Oncology Service, National Cancer Institute, National Institute of Health, Bethesda, MD, United States. Electronic address: kimc5@mail.nih.gov.
authors: Chul
authors: C
authors: Kim
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
authors: Xuehong
authors: X
authors: Zhang
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States; Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
authors: Andrew T
authors: AT
authors: Chan
authors: Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States; Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
authors: Howard D
authors: HD
authors: Sesso
authors: Department of Pathology, Children's Hospital Medical Center, Boston, MA, United States.
authors: Nader
authors: N
authors: Rifai
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States; Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States; Department of Nutrition, Harvard School of Public Health, Boston, MA, United States.
authors: Meir J
authors: MJ
authors: Stampfer
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States. Electronic address: jing.ma@channing.harvard.edu.
authors: Jing
authors: J
authors: Ma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics*; D012307:Risk Factors
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D047889:Receptors, Tumor Necrosis Factor, Type II; D002097:C-Reactive Protein; D001241:Aspirin
keywords: Aspirin; CRP; Colorectal cancer; IL-6; TNFR-2