Inflammatory and Metabolic Biomarkers and Risk of Liver and Biliary Tract Cancer

被引：170

作者：

Aleksandrova, Krasimira ^{[1
]}

Boeing, Heiner ^{[1
]}

Noethlings, Ute ^{[2
,3
]}

Jenab, Mazda ^{[4
]}

Fedirko, Veronika ^{[4
,5
,6
]}

Kaaks, Rudolf ^{[7
]}

Lukanova, Annekatrin ^{[7
,8
]}

Trichopoulou, Antonia ^{[9
,10
]}

Trichopoulos, Dimitrios ^{[10
,11
,12
]}

Boffetta, Paolo ^{[13
]}

Trepo, Elisabeth ^{[14
]}

Westhpal, Sabine ^{[15
]}

Duarte-Salles, Talita ^{[4
]}

Stepien, Magdalena ^{[4
]}

Overvad, Kim ^{[16
]}

Tjonneland, Anne ^{[17
]}

Halkjaer, Jytte ^{[17
]}

Boutron-Ruault, Marie-Christine ^{[18
,19
,20
]}

Dossus, Laure ^{[18
,19
,20
]}

Racine, Antoine ^{[18
,19
,20
]}

Lagiou, Pagona ^{[9
,11
,12
]}

Bamia, Christina ^{[9
,10
]}

Benetou, Vassiliki ^{[9
,10
]}

Agnoli, Claudia ^{[21
]}

Palli, Domenico ^{[22
]}

Panico, Salvatore ^{[23
]}

Tumino, Rosario ^{[24
]}

Vineis, Paolo ^{[25
,26
]}

Bueno-De-Mesquita, Bas ^{[27
,28
]}

Peeters, Petra H. ^{[26
,29
]}

Gram, Inger Torhild ^{[30
]}

Lund, Eiliv ^{[30
]}

Weiderpass, Elisabete ^{[30
,31
,32
,33
]}

Quiros, J. Ramon ^{[34
]}

Agudo, Antonio ^{[35
]}

Sanchez, Maria-Jose ^{[36
,37
]}

Gavrila, Diana ^{[38
,39
]}

Barricarte, Aurelio ^{[37
,39
]}

Dorronsoro, Miren ^{[40
,41
]}

Ohlsson, Bodil ^{[42
]}

Lindkvist, Bjoern ^{[43
]}

Johansson, Anders ^{[44
]}

Sund, Malin ^{[45
]}

Khaw, Kay-Tee ^{[46
]}

Wareham, Nicholas ^{[47
]}

Travis, Ruth C. ^{[48
]}

Riboli, Elio ^{[26
]}

Pischon, Tobias ^{[49
]}

机构：

[1] German Inst Human Nutr Potsdam Rehbrucke, Dept Epidemiol, D-14558 Nuthetal, Germany

[2] Univ Kiel, Inst Epidemiol, Kiel, Germany

[3] Univ Bonn, Inst Ernahrung & Lebensmittelwissenschaften, Dept Nutrit & Food Sci, Nutrit Epidemiol Unit, Bonn, Germany

[4] WHO, IARC, Lyon, France

[5] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA

[6] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA

[7] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany

[8] Umea Univ, Dept Med Biosci Pathol, Umea, Sweden

[9] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, WHO Collaborating Ctr Food & Nutr Policies, GR-11527 Athens, Greece

[10] Hellen Hlth Fdn, Athens, Greece

[11] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[12] Acad Athens, Bur Epidemiol Res, Athens, Greece

[13] Mt Sinai Hosp, Sch Med, Inst Translat Epidemiol, New York, NY 10029 USA

[14] Ctr Bioloqie Republ, Lyon, France

[15] Otto Von Guericke Univ, Inst Clin Chem, Magdeburg, Germany

[16] Aarhus Univ, Dept Publ Hlth, Epidemiol Sect, Aarhus, Denmark

[17] Danish Canc Soc Res Ctr, Copenhagen, Denmark

[18] INSERM, Ctr Res Epidemiol & Populat Hlth CESP, U1018, Nutr Hormones & Womens Hlth Team, Villejuif, France

[19] Univ Paris Sud, UMRS 1018, Villejuif, France

[20] Inst Gustave Roussy, Villejuif, France

[21] Fondaz IRCCS Ist Nazl Tumori, Nutrit Epidemiol Unit, Milan, Italy

[22] Canc Res & Prevent Inst ISPO, Mol & Nutrit Epidemiol Unit, Florence, Italy

[23] Univ Naples Federico II, Dept Clin & Expt Med, Naples, Italy

[24] M P Arezzo Hosp, Canc Registry & Histopathol Unit, Ragusa, Italy

[25] HuGef Fdn, Turin, Italy

[26] Imperial Coll, Div Epidemiol Publ Hlth & Primary Care, London, England

[27] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands

[28] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands

[29] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands

[30] Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway

[31] Canc Registry Norway, Dept Res, Oslo, Norway

[32] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[33] Samfundet Folkhalsan, Helsinki, Finland

[34] Publ Hlth Directorate, Asturias, Spain

[35] Catalan Inst Oncol, Canc Epidemiol Res Program, Unit Nutr Environm & Canc, Barcelona, Spain

[36] Andalusian Sch Publ Hlth, Granada, Spain

[37] Consortium Biomed Res Epidemiol & Publ Hlth, CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain

[38] Consejeria Sanidad & Polit Social, Dept Epidemiol, Serv Epidemiol, Murcia, Spain

[39] Navarre Publ Hlth Inst, Pamplona, Spain

[40] CIBERESP, Basque Reg Hlth Dept, San Sebastian, Spain

[41] CIBERESP, BioDonostia Res Inst, San Sebastian, Spain

[42] Lund Univ, Skane Univ Hosp, Div Internal Med, Dept Clin Sci, Malmo, Sweden

[43] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg, Sweden

[44] Umea Univ, Dept Odontol Publ Hlth & Clin Med, Umea, Sweden

[45] Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden

[46] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England

[47] Addenbrookes Hosp, Inst Metab Sci, MRC Epidemiol, Cambridge, England

[48] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England

[49] Max Delbruck Ctr Mol Med, Mol Epidemiol Grp, Berlin, Germany

来源：

HEPATOLOGY | 2014年 / 60卷 / 03期

基金：

英国医学研究理事会; 英国惠康基金; 欧洲研究理事会;

关键词：

HEPATOCELLULAR-CARCINOMA RISK; INSULIN-RESISTANCE; COLORECTAL-CANCER; ADIPONECTIN; OBESITY; LEPTIN; DISEASE; INTERLEUKIN-6; INJURY; EPIDEMIOLOGY;

D O I：

10.1002/hep.27016

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however, there are little data on the role of obesity-related biomarkers on liver cancer risk. We studied prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intrahepatic bile duct (IBD), and gallbladder and biliary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Over an average of 7.7 years, 296 participants developed HCC (n = 125), GBTC (n = 137), or IBD (n = 34). Using risk-set sampling, controls were selected in a 2: 1 ratio and matched for recruitment center, age, sex, fasting status, and time of blood collection. Baseline serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, total high-molecular-weight (HMW) adiponectin, leptin, fetuin-a, and glutamatdehydrogenase (GLDH) were measured, and incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection, and adiposity measures, higher concentrations of CRP, IL-6, C-peptide, and non-HMWadiponectin were associated with higher risk of HCC (IRR per doubling of concentrations = 1.22; 95% CI = 1.02-1.46; P = 0.03; 1.90; 95% CI = 1.30-2.77; P = 0.001; 2.25; 95% CI = 1.43-3.54; P = 0.0005; and 2.09; 95% CI = 1.19-3.67; P = 0.01, respectively). 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). The continuous net reclassification index was 0.63 for CRP, IL-6, C-peptide, and non-HMW adiponectin and 0.46 for GLDH, indicating good predictive ability of these biomarkers. Conclusion: 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.

引用

页码：858 / 871

页数：14

共 62 条

[21] FLEXIBLE REGRESSION-MODELS WITH CUBIC-SPLINES [J].

DURRLEMAN, S ;

SIMON, R .

STATISTICS IN MEDICINE, 1989, 8 (05) :551-561

[22] Leptin and cancer [J].

Garofalo, C ;

Surmacz, E .

JOURNAL OF CELLULAR PHYSIOLOGY, 2006, 207 (01) :12-22

[23] Immunity, Inflammation, and Cancer [J].

Grivennikov, Sergei I. ;

Greten, Florian R. ;

Karin, Michael .

CELL, 2010, 140 (06) :883-899

[24] Obesity and colorectal cancer: epidemiology, mechanisms and candidate genes [J].

Gunter, MJ ;

Leitzmann, MF .

JOURNAL OF NUTRITIONAL BIOCHEMISTRY, 2006, 17 (03) :145-156

[25] Fetuin A in nonalcoholic fatty liver disease: in vivo and in vitro studies [J].

Haukeland, John Willy ;

Dahl, Tuva B. ;

Yndestad, Arne ;

Gladhaug, Ivar P. ;

Loberg, Else Marit ;

Haaland, Terese ;

Konopski, Zbigniew ;

Wium, Cecilie ;

Aasheim, Erlend T. ;

Johansen, Odd Erik ;

Aukrust, Pal ;

Halvorsen, Bente ;

Birkeland, Kare I. .

EUROPEAN JOURNAL OF ENDOCRINOLOGY, 2012, 166 (03) :503-510

[26] Insulin resistance is associated with hepatocellular carcinoma in chronic hepatitis C infection [J].

Hung, Chao-Hung ;

Wang, Jing-Houng ;

Hu, Tsung-Hui ;

Chen, Chien-Hung ;

Chang, Kuo-Chin ;

Yen, Yi-Hao ;

Kuo, Yuan-Hung ;

Tsai, Ming-Chao ;

Lu, Sheng-Nan ;

Lee, Chuan-Mo .

WORLD JOURNAL OF GASTROENTEROLOGY, 2010, 16 (18) :2265-2271

[27] Association between human fetuin-A and the metabolic syndrome - Data from the Heart and Soul Study [J].

Ix, JH ;

Shlipak, MG ;

Brandenburg, VM ;

Ali, S ;

Ketteler, M ;

Whooley, MA .

CIRCULATION, 2006, 113 (14) :1760-1767

[28]

Izadi Vajihe, 2012, ISRN Oncol, V2012, P982769, DOI 10.5402/2012/982769

[29] Adiponectin and its receptors in patients with chronic hepatitis C [J].

Jonsson, JR ;

Moschen, AR ;

Hickman, IJ ;

Richardson, MM ;

Kaser, S ;

Clouston, AD ;

Powell, EE ;

Tilg, H .

JOURNAL OF HEPATOLOGY, 2005, 43 (06) :929-936

[30] Association between metabolic abnormalities and hepatitis C-related hepatocellular carcinoma [J].

Khattab, Mahmoud A. ;

Eslam, Mohammed ;

Mousa, Yousef I. ;

Ela-adawy, Nosa ;

Fathy, Shimaa ;

Shatat, Mohammed ;

Abd-Aalhalim, Hesham ;

Kamal, Amal ;

Sharawe, Mohammed A. .

ANNALS OF HEPATOLOGY, 2012, 11 (04) :487-494

← 1 2 3 4 5 6 7 →