Abstract 3441: Associations between lipopolysaccharide (LPS) and LPS pathway biomarkers and gallbladder cancer are modulated by markers of systemic inflammation
Authors: Alison L. Van Dyke, Troy J. Kemp, Amanda F. Corbel, Bin Zhu, Yu-Tang Gao, Bingsheng Wang, Asif Rashid, Ming-Chang Shen, Allan Hildesheim, Ann W. Hsing, Ligia A. Pinto, Jill Koshiol
Journal: Cancer Research (2016)

Abstract Little is known about gallbladder cancer (GBC) etiology. Gallstones (GS) are a critical factor in GBC pathogenesis. Bacterial infections, such as Salmonella Typhi and Helicobacter pylori, also may contribute to the development of GBC. We previously observed strong associations between inflammation markers and GBC vs. GS patients and hypothesized that bacterial infections may explain in part associations between GBC and inflammation. In the current study of 41 GBC cases and 124 GS patients from Shanghai, China, we evaluated relationships between GBC and the bacterial infection-related proteins plasma lipopolysaccharide (LPS) and two LPS-pathway proteins, soluble CD14 (sCD14) and lipid binding protein (LBP), as measured by ELISA. Further, we explored the extent to which these associations were mediated through systemic inflammation. Logistic regression was conducted to assess associations of GBC with plasma LPS, sCD14, and LBP levels. To evaluate mediation through inflammation, an inflammation score was calculated by summing the value of 15 previously measured GBC-associated serum inflammation markers (β-coefficient multiplied by 1 if above the median or 0 if below the median) and included in the models. sCD14 and LBP levels (above vs. below the median) were strongly associated with GBC [Odds Ratio (95% Confidence Interval): 2.75 (1.27-6.29) for sCD14 and 2.83 (1.32-6.46) for LBP]. The highest vs. lowest tertiles of sCD14 and LBP were associated with a five-fold increased risk of GBC. These associations were attenuated when the inflammation score was entered into the model. Plasma LPS demonstrated a borderline association after adjustment for inflammation score [OR (95% CI): 2.46 (0.96-6.56)]. In contrast, the ORs for inflammation score remained &amp;gt;20 after adjusting for each bacteria-related marker. These findings suggest that bacterial infections may contribute to GBC etiopathogenesis through inflammatory pathways. LPS, sCD14, and LBP and Gallbladder Cancer Relative to Gallstone ControlsLPSSex &amp; Age Adjusted OR (95% CI)Sex, Age, &amp; Inflammation Score Adjusted OR (95% CI)Detectable Level1.001.00Undetectable Level1.81 (0.85-3.80)2.46 (0.96-6.56)sCD14Sex, Age, &amp; Batch Adjusted OR (95% CI)Sex, Age, Batch, &amp; Inflammation Score Adjusted OR (95% CI)Below Median1.001.00Above Median2.75 (1.27-6.29)1.05 (0.39-2.83)1st Tertile1.001.002nd Tertile1.42 (0.45-4.71)0.44 (0.10-1.80)3rd Tertile5.27 (1.98-16.06)1.37 (0.38-5.04)p-trend0.00060.25LBPSex, Age, &amp; Batch Adjusted OR (95% CI)Sex, Age, Batch, &amp; Inflammation Score Adjusted OR (95% CI)Below Median1.001.00Above Median2.83 (1.32-6.46)1.63 (0.64-4.28)1st Tertile1.001.002nd Tertile1.95 (0.61-6.99)1.53 (0.37-7.01)3rd Tertile5.01 (1.84-16.25)2.09 (0.58-8.71)p-trend0.00080.25 Citation Format: Alison L. Van Dyke, Troy J. Kemp, Amanda F. Corbel, Bin Zhu, Yu-Tang Gao, Bingsheng Wang, Asif Rashid, Ming-Chang Shen, Allan Hildesheim, Ann W. Hsing, Ligia A. Pinto, Jill Koshiol. Associations between lipopolysaccharide (LPS) and LPS pathway biomarkers and gallbladder cancer are modulated by markers of systemic inflammation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3441.