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Inflammatory and metabolic biomarkers and risk of liver and biliary tract cancer.

Aleksandrova K, Boeing H, Nöthlings U, Jenab M, Fedirko V, Kaaks R, Lukanova A, Trichopoulou A, Trichopoulos D, Boffetta P, Trepo E, Westhpal S, Duarte-Salles T, Stepien M, Overvad K, Tjønneland A, Halkjaer J, Boutron-Ruault MC, Dossus L, Racine A, Lagiou P, Bamia C, Benetou V, Agnoli C, Palli D, Panico S, Tumino R, Vineis P, Bueno-de-Mesquita B, Peeters PH, Gram IT, Lund E, Weiderpass E, Quirós JR, Agudo A, Sánchez MJ, Gavrila D, Barricarte A, Dorronsoro M, Ohlsson B, Lindkvist B, Johansson A, Sund M, Khaw KT, Wareham N, Travis RC, Riboli E, Pischon T - Hepatology (2014)

Bottom Line: CRP was associated also with risk of GBTC (IRR=1.22; 95% CI=1.05-1.42; P=0.01).GLDH was associated with risks of HCC (IRR=1.62; 95% CI=1.25-2.11; P=0.0003) and IBD (IRR=10.5; 95% CI=2.20-50.90; P=0.003).Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.

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Predictive ability of inflammatory and metabolic biomarkers and GLDH beyond the multivariable adjusted model and AFP levels. aThe biomarkers included in the model have been associated with HCC risk. These include CRP, Il-6, C-peptide, and non-HMW adiponectin. bMultivariable model taking into account matching factors: study center; gender; age (±12 months); date (±2 months); fasting status (<3, 3-6, or >6 hours); and time of the day (±3 hours) at blood collection. Women were additionally matched according to menopausal status (pre-, peri- [unknown], or postmenopausal) and exogenous hormone use (yes, no, or missing) at blood donation. Further adjusted for education (no school degree or primary school, secondary school, high school, or missing), smoking (never, former, current, or missing), alcohol at baseline, drinking status at baseline (nondrinker or drinker), diabetes (no, yes, or missing), coffee (g/day), HBsAg/anti-HCV (negative, positive, or missing), BMI, and WHtR adjusted for BMI. Note: Analyses were based on overall 293 cases and 581 controls for adiponectin, 293 cases and 577 controls for CRP and GLDH, and 277 cases and 549 controls for C-peptide. For this analysis, missing values for IL-6 (33 cases and 72 controls) were substituted with sex- and case-control–specific median values.
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fig03: Predictive ability of inflammatory and metabolic biomarkers and GLDH beyond the multivariable adjusted model and AFP levels. aThe biomarkers included in the model have been associated with HCC risk. These include CRP, Il-6, C-peptide, and non-HMW adiponectin. bMultivariable model taking into account matching factors: study center; gender; age (±12 months); date (±2 months); fasting status (<3, 3-6, or >6 hours); and time of the day (±3 hours) at blood collection. Women were additionally matched according to menopausal status (pre-, peri- [unknown], or postmenopausal) and exogenous hormone use (yes, no, or missing) at blood donation. Further adjusted for education (no school degree or primary school, secondary school, high school, or missing), smoking (never, former, current, or missing), alcohol at baseline, drinking status at baseline (nondrinker or drinker), diabetes (no, yes, or missing), coffee (g/day), HBsAg/anti-HCV (negative, positive, or missing), BMI, and WHtR adjusted for BMI. Note: Analyses were based on overall 293 cases and 581 controls for adiponectin, 293 cases and 577 controls for CRP and GLDH, and 277 cases and 549 controls for C-peptide. For this analysis, missing values for IL-6 (33 cases and 72 controls) were substituted with sex- and case-control–specific median values.

Mentions: Addition of CRP, IL-6, C-peptide, and non-HMW adiponectin to the multivariable model significantly increased the AUC for the prediction of HCC from 0.766 to 0.876, whereas addition of the liver damage marker, GLDH, to the multivariable model raised the AUC from 0.769 to 0.813 (Fig. 2). When inflammatory and metabolic biomarkers were added to the model, the IDI was 0.81 and the NRI was 0.63 (P < 0.0001), indicating strong reclassification improvement, whereas when GLDH was added to the model, the IDI was 0.24 and the NRI was 0.46 (P = 0.07), indicating moderate improvement. Addition of CRP, IL-6, C-peptide, and non-HMW adiponectin to the multivariable model that additionally included AFP significantly increased the AUC for the prediction of HCC from 0.777 to 0.855; GLDH increased the AUC from 0.803 to 0.836 (Fig. 3). When inflammatory and metabolic biomarkers were added to the model, the IDI was 0.43, and NRI(>0) was 0.44 (P = 0.0004), indicating moderate reclassification improvement; when GLDH was added to the model, the IDI was 0.10 and the NRI(>0) was 0.21 (P = 0.29), indicating weak improvement (Fig. 3).


Inflammatory and metabolic biomarkers and risk of liver and biliary tract cancer.

Aleksandrova K, Boeing H, Nöthlings U, Jenab M, Fedirko V, Kaaks R, Lukanova A, Trichopoulou A, Trichopoulos D, Boffetta P, Trepo E, Westhpal S, Duarte-Salles T, Stepien M, Overvad K, Tjønneland A, Halkjaer J, Boutron-Ruault MC, Dossus L, Racine A, Lagiou P, Bamia C, Benetou V, Agnoli C, Palli D, Panico S, Tumino R, Vineis P, Bueno-de-Mesquita B, Peeters PH, Gram IT, Lund E, Weiderpass E, Quirós JR, Agudo A, Sánchez MJ, Gavrila D, Barricarte A, Dorronsoro M, Ohlsson B, Lindkvist B, Johansson A, Sund M, Khaw KT, Wareham N, Travis RC, Riboli E, Pischon T - Hepatology (2014)

Predictive ability of inflammatory and metabolic biomarkers and GLDH beyond the multivariable adjusted model and AFP levels. aThe biomarkers included in the model have been associated with HCC risk. These include CRP, Il-6, C-peptide, and non-HMW adiponectin. bMultivariable model taking into account matching factors: study center; gender; age (±12 months); date (±2 months); fasting status (<3, 3-6, or >6 hours); and time of the day (±3 hours) at blood collection. Women were additionally matched according to menopausal status (pre-, peri- [unknown], or postmenopausal) and exogenous hormone use (yes, no, or missing) at blood donation. Further adjusted for education (no school degree or primary school, secondary school, high school, or missing), smoking (never, former, current, or missing), alcohol at baseline, drinking status at baseline (nondrinker or drinker), diabetes (no, yes, or missing), coffee (g/day), HBsAg/anti-HCV (negative, positive, or missing), BMI, and WHtR adjusted for BMI. Note: Analyses were based on overall 293 cases and 581 controls for adiponectin, 293 cases and 577 controls for CRP and GLDH, and 277 cases and 549 controls for C-peptide. For this analysis, missing values for IL-6 (33 cases and 72 controls) were substituted with sex- and case-control–specific median values.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231978&req=5

fig03: Predictive ability of inflammatory and metabolic biomarkers and GLDH beyond the multivariable adjusted model and AFP levels. aThe biomarkers included in the model have been associated with HCC risk. These include CRP, Il-6, C-peptide, and non-HMW adiponectin. bMultivariable model taking into account matching factors: study center; gender; age (±12 months); date (±2 months); fasting status (<3, 3-6, or >6 hours); and time of the day (±3 hours) at blood collection. Women were additionally matched according to menopausal status (pre-, peri- [unknown], or postmenopausal) and exogenous hormone use (yes, no, or missing) at blood donation. Further adjusted for education (no school degree or primary school, secondary school, high school, or missing), smoking (never, former, current, or missing), alcohol at baseline, drinking status at baseline (nondrinker or drinker), diabetes (no, yes, or missing), coffee (g/day), HBsAg/anti-HCV (negative, positive, or missing), BMI, and WHtR adjusted for BMI. Note: Analyses were based on overall 293 cases and 581 controls for adiponectin, 293 cases and 577 controls for CRP and GLDH, and 277 cases and 549 controls for C-peptide. For this analysis, missing values for IL-6 (33 cases and 72 controls) were substituted with sex- and case-control–specific median values.
Mentions: Addition of CRP, IL-6, C-peptide, and non-HMW adiponectin to the multivariable model significantly increased the AUC for the prediction of HCC from 0.766 to 0.876, whereas addition of the liver damage marker, GLDH, to the multivariable model raised the AUC from 0.769 to 0.813 (Fig. 2). When inflammatory and metabolic biomarkers were added to the model, the IDI was 0.81 and the NRI was 0.63 (P < 0.0001), indicating strong reclassification improvement, whereas when GLDH was added to the model, the IDI was 0.24 and the NRI was 0.46 (P = 0.07), indicating moderate improvement. Addition of CRP, IL-6, C-peptide, and non-HMW adiponectin to the multivariable model that additionally included AFP significantly increased the AUC for the prediction of HCC from 0.777 to 0.855; GLDH increased the AUC from 0.803 to 0.836 (Fig. 3). When inflammatory and metabolic biomarkers were added to the model, the IDI was 0.43, and NRI(>0) was 0.44 (P = 0.0004), indicating moderate reclassification improvement; when GLDH was added to the model, the IDI was 0.10 and the NRI(>0) was 0.21 (P = 0.29), indicating weak improvement (Fig. 3).

Bottom Line: CRP was associated also with risk of GBTC (IRR=1.22; 95% CI=1.05-1.42; P=0.01).GLDH was associated with risks of HCC (IRR=1.62; 95% CI=1.25-2.11; P=0.0003) and IBD (IRR=10.5; 95% CI=2.20-50.90; P=0.003).Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.

Show MeSH
Related in: MedlinePlus