title: Association of inflammatory and other immune markers with gallbladder cancer: Results from two independent case-control studies.
abstract: Most gallbladder cancer (GBC) cases arise in the context of gallstones, which cause inflammation, but few gallstone patients develop GBC. We explored inflammation/immune-related markers measured in bile and serum in GBC cases compared to gallstone patients to better understand how inflammatory patterns in these two conditions differ. We measured 65 immune-related markers in serum and bile from 41 GBC cases and 127 gallstone patients from Shanghai, China, and calculated age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for GBC versus gallstones. We then focused on the markers that were significantly elevated in bile and serum to replicate the findings in serum from 35 GBC cases and 31 gallstone controls from Chile. Comparing the highest versus lowest quantile, 15 markers (23%) were elevated in both serum and bile from GBC versus gallstone patients in the Shanghai study (p<0.05). The strongest OR was for CXCL8 (interleukin-8) in serum (96.8, 95% CI: 11.9-790.2). Of these 15 markers, 6 were also significantly elevated in serum from Chile (CCL20, C-reactive protein, CXCL8, CXCL10, resistin, serum amyloid A). Pooled ORs from Shanghai and Chile for these 6 markers ranged from 7.2 (95% CI: 2.8-18.4) for CXCL10 to 58.2 (95% CI: 12.4-273.0) for CXCL8. GBC is associated with inflammation above and beyond that generated by gallstones alone. This local inflammatory process is reflected systemically. Future longitudinal studies are needed to identify the key players in cancer development, which may guide translational efforts to identify individuals at high risk of developing GBC.
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, MD, USA. Electronic address: koshiolj@mail.nih.gov.
authors.forename: Jill
authors.initials: J
authors.lastname: Koshiol
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, MD, USA; Real World Data Science (RWD-S) Oncology, Roche, Basel, Switzerland(1).
authors.forename: Felipe
authors.initials: F
authors.lastname: Castro
authors.affiliation: HPV Immunology Laboratory, Frederick National Laboratory for Cancer Research, Leidos, Biomedical Research, Inc, Frederick, MD, USA.
authors.forename: Troy J
authors.initials: TJ
authors.lastname: Kemp
authors.affiliation: Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.affiliation: School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; Advanced Center for Chronic Diseases (ACCDiS), FONDAP, Santiago, Chile.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Roa
authors.affiliation: Department of General Surgery, Zhongshan Hospital, School of Medicine, Fudan University, Shanghai, China.
authors.forename: Bingsheng
authors.initials: B
authors.lastname: Wang
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, MD, USA; Texas Department of State Health Services, Austin, TX, USA(1).
authors.forename: Leticia
authors.initials: L
authors.lastname: Nogueira
authors.affiliation: Hospital Dr. Hernan Henríquez Aravena, Temuco, Chile; Anatomic Pathology Department, Medicine Faculty, Universidad de La Frontera, Temuco, Chile.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Araya
authors.affiliation: Department of Pathology, Shanghai Cancer Center, Fudan University, Shanghai, China.
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Shen
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Asif
authors.initials: A
authors.lastname: Rashid
authors.affiliation: Stanford Cancer Institute, Palo Alto, CA, USA; Department of Health Research and Policy, Stanford School of Medicine, Palo Alto, CA, USA.
authors.forename: Ann W
authors.initials: AW
authors.lastname: Hsing
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, MD, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.affiliation: School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; Advanced Center for Chronic Diseases (ACCDiS), FONDAP, Santiago, Chile.
authors.forename: Catterina
authors.initials: C
authors.lastname: Ferreccio
authors.affiliation: Biostastitics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, MD, USA.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.affiliation: HPV Immunology Laboratory, Frederick National Laboratory for Cancer Research, Leidos, Biomedical Research, Inc, Frederick, MD, USA.
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Pinto
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism*; D016022:Case-Control Studies; D018925:Chemokines / Q000097:blood*; D005260:Female; D005706:Gallbladder Neoplasms / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D052243:Resistin / Q000097:blood*; D000685:Serum Amyloid A Protein / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018925:Chemokines; C499624:RETN protein, human; D052243:Resistin; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein
keywords: Gallbladder cancer; Local inflammation; Systemic inflammation