title: Associations of Coffee Drinking with Systemic Immune and Inflammatory Markers.
abstract: BACKGROUND
  Coffee drinking has been inversely associated with mortality as well as cancers of the endometrium, colon, skin, prostate, and liver. Improved insulin sensitivity and reduced inflammation are among the hypothesized mechanisms by which coffee drinking may affect cancer risk; however, associations between coffee drinking and systemic levels of immune and inflammatory markers have not been well characterized.
  
  
  METHODS
  We used Luminex bead-based assays to measure serum levels of 77 immune and inflammatory markers in 1,728 older non-Hispanic Whites. Usual coffee intake was self-reported using a food frequency questionnaire. We used weighted multivariable logistic regression models to examine associations between coffee and dichotomized marker levels. We conducted statistical trend tests by modeling the median value of each coffee category and applied a 20% false discovery rate criterion to P values.
  
  
  RESULTS
  Ten of the 77 markers were nominally associated (P trend < 0.05) with coffee drinking. Five markers withstood correction for multiple comparisons and included aspects of the host response namely chemotaxis of monocytes/macrophages (IFNγ, CX3CL1/fractalkine, CCL4/MIP-1β), proinflammatory cytokines (sTNFRII), and regulators of cell growth (FGF-2). Heavy coffee drinkers had lower circulating levels of IFNγ [odds ratios (OR), 0.35; 95% confidence intervals (CI), 0.16-0.75], CX3CL1/fractalkine (OR, 0.25; 95% CI, 0.10-0.64), CCL4/MIP-1β (OR, 0.48; 95% CI, 0.24-0.99), FGF-2 (OR, 0.62; 95% CI, 0.28-1.38), and sTNFRII (OR, 0.34; 95% CI, 0.15-0.79) than non-coffee drinkers.
  
  
  CONCLUSIONS
  Lower circulating levels of inflammatory markers among coffee drinkers may partially mediate previously observed associations of coffee with cancer and other chronic diseases.
  
  
  CONCLUSIONS
  Validation studies, ideally controlled feeding trials, are needed to confirm these associations.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut. erikka.loftfield@nih.gov.
authors.forename: Erikka
authors.initials: E
authors.lastname: Loftfield
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Meredith S
authors.initials: MS
authors.lastname: Shiels
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Barry I
authors.initials: BI
authors.lastname: Graubard
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Hormuzd A
authors.initials: HA
authors.lastname: Katki
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Chaturvedi
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Britton
authors.initials: B
authors.lastname: Trabert
authors.affiliation: HPV Immunology Laboratory, Leidos Biomedical Research, Inc., SAIC-Frederick/NCI-Frederick, Frederick, Maryland.
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Pinto
authors.affiliation: HPV Immunology Laboratory, Leidos Biomedical Research, Inc., SAIC-Frederick/NCI-Frederick, Frederick, Maryland.
authors.forename: Troy J
authors.initials: TJ
authors.lastname: Kemp
authors.affiliation: Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut. Yale Cancer Center, New Haven, Connecticut.
authors.forename: Fatma M
authors.initials: FM
authors.lastname: Shebl
authors.affiliation: Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut. Yale Cancer Center, New Haven, Connecticut.
authors.forename: Susan T
authors.initials: ST
authors.lastname: Mayne
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.affiliation: Ontario Institute for Cancer Research, Toronto, Canada.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Purdue
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Neal D
authors.initials: ND
authors.lastname: Freedman
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D003069:Coffee; D003430:Cross-Sectional Studies; D005247:Feeding Behavior; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control; D016017:Odds Ratio; D015995:Prevalence; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D003069:Coffee