The association of coffee intake with liver cancer risk is mediated by biomarkers of inflammation and hepatocellular injury: data from the European Prospective Investigation into Cancer and Nutrition

被引：64

作者：

Aleksandrova, Krasimira ^{[1
]}

Bamia, Christina ^{[2
,3
]}

Drogan, Dagmar ^{[1
]}

Lagiou, Pagona ^{[2
,4
,5
]}

Trichopoulou, Antonia ^{[2
,3
]}

Jenab, Mazda ^{[6
]}

Fedirko, Veronika ^{[7
,8
]}

Romieu, Isabelle ^{[6
]}

Bueno-de-Mesquita, H. Bas ^{[9
,10
,11
,12
]}

Pischon, Tobias ^{[13
]}

Tsilidis, Kostas ^{[14
]}

Overvad, Kim ^{[15
]}

Tjonneland, Anne ^{[16
]}

Bouton-Ruault, Marie-Christine ^{[17
,18
,19
]}

Dossus, Laure ^{[17
,18
,19
]}

Racine, Antoine ^{[17
,18
,19
]}

Kaaks, Rudolf ^{[20
]}

Kuehn, Tilman ^{[20
]}

Tsironis, Christos ^{[3
]}

Papatesta, Eleni-Maria ^{[3
]}

Saitakis, George ^{[3
]}

Palli, Domenico ^{[21
]}

Panico, Salvatore ^{[22
]}

Grioni, Sara ^{[23
]}

Tumino, Rosario ^{[24
]}

Vineis, Paolo ^{[11
,25
]}

Peeters, Petra H. ^{[11
,26
]}

Weiderpass, Elisabete ^{[27
,28
,29
,30
]}

Lukic, Marko ^{[27
]}

Braaten, Tonje ^{[27
]}

Ramon Quiros, J. ^{[31
]}

Lujan-Barroso, Leila ^{[32
]}

Sanchez, Mara-Jose ^{[33
]}

Chilarque, Maria-Dolores ^{[34
]}

Ardanas, Eva ^{[35
]}

Dorronsoro, Miren ^{[36
]}

Nilsson, Lena Maria ^{[37
]}

Sund, Malin ^{[38
]}

Wallstrom, Peter ^{[39
]}

Ohlsson, Bodil ^{[40
]}

Bradbury, Kathryn E. ^{[41
]}

Khaw, Kay-Tee ^{[42
]}

Wareham, Nick ^{[43
]}

Stepien, Magdalena ^{[6
]}

Duarte-Salles, Talita ^{[6
]}

Assi, Nada ^{[6
]}

Murphy, Neil ^{[11
]}

Gunter, Marc J. ^{[11
]}

Riboli, Elio ^{[11
]}

Boeing, Heiner ^{[1
]}

机构：

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

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

[3] Hellen Hlth Fdn, Athens, Greece

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

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

[6] Int Agcy Res Canc, F-69372 Lyon, France

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

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

[9] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands

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

[11] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England

[12] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur, Malaysia

[13] Max Delbrueck Ctr Mol Med, Mol Epidemiol Grp, Berlin, Germany

[14] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece

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

[16] Danish Canc Soc Res Ctr, Diet Genes & Environm, Copenhagen, Denmark

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

[18] Univ Paris 11, Villejuif, France

[19] IGR, Villejuif, France

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

[21] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy

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

[23] Ist Nazl Tumori, Fdn IRCCS, Epidemiol & Prevent Unit, I-20133 Milan, Italy

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

[25] HuGeF Fdn, Turin, Italy

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

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

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

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

[30] Folkhalsan Res Ctr, Genet Epidemiol Grp, Helsinki, Finland

[31] Publ Hlth Directorate, Oviedo, Spain

[32] Bellvitge Biomed Res Inst, Catalan Inst Oncol, Canc Epidemiol Res Program, Unit Nutr & Canc, Barcelona, Spain

[33] Univ Granada, Hosp Univ Granada, Escuela Andaluza Salud Publ, Inst Invest Biosanitaria Ibs GRANADA, Granada, Spain

[34] IMIB Arrixaca, Murcia Reg Hlth Author, Dept Epidemiol, Murcia, Spain

[35] Navarre Publ Hlth Inst, Pamplona, Spain

[36] Basque Reg Hlth Dept, Publ Hlth Div Gipuzkoa, Epidemiol & Hlth Informat, San Sebastian, Spain

[37] Umea Univ, Arctic Res Ctr, Umea, Sweden

[38] Umea Univ, Dept Surg & Perioperat Sci Surg & Publ Hlth, Nutr Res, Umea, Sweden

[39] Lund Univ, Dept Clin Sci, Clin Res Ctr, Malmo, Sweden

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

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

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

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

来源：

AMERICAN JOURNAL OF CLINICAL NUTRITION | 2015年 / 102卷 / 06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：

biomarkers; coffee; European Prospective Investigation into Cancer and Nutrition; liver cancer; mediation; GAMMA-GLUTAMYL-TRANSFERASE; C-REACTIVE PROTEIN; DECAFFEINATED COFFEE; CONSUMPTION; HEPATITIS; CARCINOMA; DISEASE; NAFLD; IRON; VALIDATION;

D O I：

10.3945/ajcn.115.116095

中图分类号：

R15 [营养卫生、食品卫生]; TS201 [基础科学];

学科分类号：

100403 ;

摘要：

Background: Higher coffee intake has been purportedly related to a lower risk of liver cancer. However, it remains unclear whether this association may be accounted for by specific biological mechanisms. Objective: We aimed to evaluate the potential mediating roles of inflammatory, metabolic, liver injury, and iron metabolism biomarkers on the association between coffee intake and the primary form of liver cancer-hepatocellular carcinoma (HCC). Design: We conducted a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition among 125 incident HCC cases matched to 250 controls using an incidence-density sampling procedure. The association of coffee intake with HCC risk was evaluated by using multivariable-adjusted conditional logistic regression that accounted for smoking, alcohol consumption, hepatitis infection, and other established liver cancer risk factors. The mediating effects of 21 biomarkers were evaluated on the basis of percentage changes and associated 95% CIs in the estimated regression coefficients of models with and without adjustment for biomarkers individually and in combination. Results: The multivariable-adjusted RR of having >= 4 cups (600mL) coffee/d compared with <2 cups (300 mL)/d was 0.25 (95% CI: 0.11, 0.62; P-trend = 0.006). A statistically significant attenuation of the association between coffee intake and HCC risk and thereby suspected mediation was confirmed for the inflammatory biomarker IL-6 and for the biomarkers of hepatocellular injury glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), and total bilirubin, which-in combination-attenuated the regression coefficients by 72% (95% CI: 7%, 239%). Of the investigated biomarkers, IL-6, AST, and GGT produced the highest change in the regression coefficients: 40%, 56%, and 60%, respectively. Conclusion: These data suggest that the inverse association of coffee intake with HCC risk was partly accounted for by biomarkers of inflammation and hepatocellular injury.

引用

页码：1498 / 1508

页数：11

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