title: Lipopolysaccharide-pathway proteins are associated with gallbladder cancer among adults in Shanghai, China with mediation by systemic inflammation.
abstract: We examined inflammation as a mediator of associations between bacterial infection markers and gallbladder cancer (GBC).
  
  
  
  Bacterial response proteins (lipopolysaccharide [LPS], soluble cluster of differentiation 14 [sCD14], and LPS-binding protein [LBP]) were measured in 40 GBC cases and 126 gallstone controls with data on 63 serum inflammation markers. The relationships of LPS, LBP, and sCD14 with GBC were examined by logistic regression, which also was used to evaluate whether these associations are influenced by systemic inflammation as measured by a combinatorial inflammation score.
  
  
  
  The third versus the first tertiles of sCD14 and of LBP were associated with an increased GBC risk (odds ratio [95% confidence interval]: 5.41 [2.00-16.75] for sCD14, and 6.49 [2.24-23.79] for LBP). sCD14 and LBP were strongly associated with inflammation score (above vs. below the median), which itself was associated with a more than 21-fold increased risk of GBC for the third versus first tertiles. Associations between GBC and sCD14 and LBP were markedly attenuated when the inflammation score was included in the model. While LPS was not associated with GBC or inflammation, only 35% of cases and 22% of controls had detectable levels.
  
  
  
  These findings suggest that these LPS-pathway proteins are associated with GBC via inflammation-related pathways.
authors: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute (NCI), Bethesda, MD. Electronic address: alison.vandyke@nih.gov.
authors: Alison L
authors: AL
authors: Van Dyke
authors: HPV Immunology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD.
authors: Troy J
authors: TJ
authors: Kemp
authors: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute (NCI), Bethesda, MD.
authors: Amanda F
authors: AF
authors: Corbel
authors: Biostatistics Branch, DCEG, NCI, Bethesda, MD.
authors: Bin
authors: B
authors: Zhu
authors: Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
authors: Yu-Tang
authors: YT
authors: Gao
authors: Department of General Surgery, Zhongshan Hospital, School of Medicine, Fudan University, Shanghai, China.
authors: Bing-Sheng
authors: BS
authors: Wang
authors: Department of Pathology, MD Anderson Cancer Center, Houston, TX.
authors: Asif
authors: A
authors: Rashid
authors: Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China; Department of Pathology, Cancer Hospital, Fudan University, Shanghai, China.
authors: Ming-Chang
authors: MC
authors: Shen
authors: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute (NCI), Bethesda, MD.
authors: Allan
authors: A
authors: Hildesheim
authors: Center for Innovative Global Health, Stanford Cancer Institute, Stanford University, Stanford, CA.
authors: Ann W
authors: AW
authors: Hsing
authors: HPV Immunology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD.
authors: Ligia A
authors: LA
authors: Pinto
authors: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute (NCI), Bethesda, MD.
authors: Jill
authors: J
authors: Koshiol
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000328:Adult; D017677:Age Distribution; D014408:Biomarkers, Tumor / Q000097:blood*; D002352:Carrier Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D002764:Cholecystitis / Q000097:blood* / Q000453:epidemiology; D016208:Databases, Factual; D005260:Female; D005706:Gallbladder Neoplasms / Q000097:blood* / Q000453:epidemiology* / Q000473:pathology; D006801:Humans; D015994:Incidence; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D012189:Retrospective Studies; D018570:Risk Assessment; D017678:Sex Distribution; D016019:Survival Analysis; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D000099231:Lipopolysaccharide-Binding Protein
keywords: Gallbladder cancer; Inflammation; Lipopolysaccharide-pathway; Mediation analysis