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Ann Epidemiol. 2016 Oct;26(10):704-709. doi: 10.1016/j.annepidem.2016.08.009. Epub 2016 Aug 31.

Lipopolysaccharide-pathway proteins are associated with gallbladder cancer among adults in Shanghai, China with mediation by systemic inflammation.

Author information

1
Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute (NCI), Bethesda, MD. Electronic address: alison.vandyke@nih.gov.
2
HPV Immunology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD.
3
Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute (NCI), Bethesda, MD.
4
Biostatistics Branch, DCEG, NCI, Bethesda, MD.
5
Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
6
Department of General Surgery, Zhongshan Hospital, School of Medicine, Fudan University, Shanghai, China.
7
Department of Pathology, MD Anderson Cancer Center, Houston, TX.
8
Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China; Department of Pathology, Cancer Hospital, Fudan University, Shanghai, China.
9
Center for Innovative Global Health, Stanford Cancer Institute, Stanford University, Stanford, CA.

Abstract

PURPOSE:

We examined inflammation as a mediator of associations between bacterial infection markers and gallbladder cancer (GBC).

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

These findings suggest that these LPS-pathway proteins are associated with GBC via inflammation-related pathways.

KEYWORDS:

Gallbladder cancer; Inflammation; Lipopolysaccharide-pathway; Mediation analysis

PMID:
27793274
PMCID:
PMC5123694
DOI:
10.1016/j.annepidem.2016.08.009
[Indexed for MEDLINE]
Free PMC Article

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