Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)

被引：56

作者：

Aleksandrova, Krasimira ^{[1
]}

Jenab, Mazda ^{[2
]}

Bueno-de-Mesquita, H. Bas ^{[3
,4
]}

Fedirko, Veronika ^{[2
,5
,6
]}

Kaaks, Rudolf ^{[7
]}

Lukanova, Annekatrin ^{[7
,8
]}

van Duijnhoven, Franzel J. B. ^{[3
,9
]}

Jansen, Eugene ^{[3
]}

Rinaldi, Sabina ^{[2
]}

Romieu, Isabelle ^{[2
]}

Ferrari, Pietro ^{[2
]}

Murphy, Neil ^{[10
]}

Gunter, Marc J. ^{[10
]}

Riboli, Elio ^{[10
]}

Westhpal, Sabine ^{[11
]}

Overvad, Kim ^{[12
]}

Tjonneland, Anne ^{[13
]}

Halkjaer, Jytte ^{[13
]}

Boutron-Ruault, Marie-Christine ^{[14
,15
,16
]}

Dossus, Laure ^{[14
,15
,16
]}

Racine, Antoine ^{[14
,15
,16
]}

Trichopoulou, Antonia ^{[17
,18
]}

Bamia, Christina ^{[18
]}

Orfanos, Philippos ^{[18
]}

Agnoli, Claudia ^{[19
]}

Palli, Domenico ^{[20
]}

Panico, Salvatore ^{[21
]}

Tumino, Rosario ^{[22
,23
]}

Vineis, Paolo ^{[10
,24
]}

Peeters, Petra H. ^{[10
,25
]}

Duell, Eric J. ^{[26
]}

Molina-Montes, Esther ^{[27
,28
,29
]}

Ramon Quiros, J. ^{[30
]}

Dorronsoro, Miren ^{[31
]}

Chirlaque, Maria-Dolores ^{[28
,32
]}

Barricarte, Aurelio ^{[33
]}

Ljuslinder, Ingrid ^{[34
]}

Palmqvist, Richard ^{[35
]}

Travis, Ruth C. ^{[36
]}

Khaw, Kay-Tee ^{[37
]}

Wareham, Nicholas ^{[38
]}

Pischon, Tobias ^{[39
]}

Boeing, Heiner ^{[1
]}

机构：

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

[2] Int Agcy Res Canc IARC WHO, Lyon, France

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

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

[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] Wageningen Univ, Div Human Nutr, NL-6700 AP Wageningen, Netherlands

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

[11] Univ Magdeburg, Inst Clin Chem, D-39106 Magdeburg, Germany

[12] Aarhus Univ, Dept Epidemiol, Sch Publ Hlth, Aarhus, Denmark

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

[14] Ctr Res Epidemiol & Populat Hlth CESP, INSERM, Nutr Hormones & Womens Hlth Team, U1018, F-94805 Villejuif, France

[15] Univ Paris 11, UMRS 1018, F-94805 Villejuif, France

[16] IGR, F-94805 Villejuif, France

[17] Hellen Hlth Fdn, Athens, Greece

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

[19] Fdn IRCCS Ist Nazl Tumori, Nutr Epidemiol Unit, Milan, Italy

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

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

[22] MP Arezzo Hosp, Canc Registry, Ragusa, Italy

[23] MP Arezzo Hosp, Histopathol Unit, Ragusa, Italy

[24] HuGeF Fdn, Turin, Italy

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

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

[27] Escuela Andaluza Salud Publ, Granada, Spain

[28] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain

[29] Inst Invest Biosanitaria Granada Granada Bs, Granada, Spain

[30] Publ Hlth Directorate, Asturias, Spain

[31] Basque Reg Hlth Dept, Publ Hlth Div Gipuzkoa, San Sebastian, Spain

[32] Murcia Reg Hlth Author, Dept Epidemiol, Murcia, Spain

[33] Navarre Publ Hlth Inst, Pamplona, Spain

[34] Umea Univ Hosp, Dept Radiat Sci, S-90185 Umea, Sweden

[35] Umea Univ, Dept Med Biosci, Umea, Sweden

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

[37] Univ Cambridge, Addenbrookes Hosp, Clin Gerontol Unit, Sch Clin Med, Cambridge CB2 2QQ, England

[38] Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Inst Metab Sci, Cambridge, England

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

来源：

EUROPEAN JOURNAL OF EPIDEMIOLOGY | 2014年 / 29卷 / 04期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

Colorectal cancer; Biomarker patterns; Inflammatory and metabolic pathways; Principal component analysis; European Prospective Investigation into Cancer and Nutrition (EPIC); SOLUBLE LEPTIN RECEPTOR; DENSITY-LIPOPROTEIN CHOLESTEROL; C-REACTIVE PROTEIN; INSULIN-RESISTANCE; OXIDATIVE STRESS; HDL-CHOLESTEROL; PLASMA ADIPONECTIN; BINDING-PROTEINS; ADIPOSE-TISSUE; RECTAL-CANCER;

D O I：

10.1007/s10654-014-9901-8

中图分类号：

R1 [预防医学、卫生学];

学科分类号：

100235 [预防医学];

摘要：

A number of biomarkers of inflammatory and metabolic pathways are individually related to higher risk of colorectal cancer (CRC); however, the association between biomarker patterns and CRC incidence has not been previously evaluated. Our study investigates the association of biomarker patterns with CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). During median follow-up time of 7.0 (3.7-9.4) years, 1,260 incident CRC cases occurred and were matched to 1,260 controls using risk-set sampling. Pre-diagnostic measurements of C-peptide, glycated hemoglobin, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), reactive oxygen metabolites (ROM), insulin-like growth factor 1, adiponectin, leptin and soluble leptin receptor (sOB-R) were used to derive biomarker patterns from principal component analysis (PCA). The relation with CRC incidence was assessed using conditional logistic regression models. We identified four biomarker patterns 'HDL-C/Adiponectin fractions', 'ROM/CRP', 'TG/C-peptide' and 'leptin/sOB-R' to explain 60 % of the overall biomarker variance. In multivariable-adjusted logistic regression, the 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' patterns were associated with CRC risk [for the highest quartile vs the lowest, incidence rate ratio (IRR) = 0.69, 95 % CI 0.51-0.93, P-trend = 0.01; IRR = 1.70, 95 % CI 1.30-2.23, P-trend = 0.002; and IRR = 0.79, 95 % CI 0.58-1.07; P-trend = 0.05, respectively]. In contrast, the 'TG/C-peptide' pattern was not associated with CRC risk (IRR = 0.75, 95 % CI 0.56-1.00, P-trend = 0.24). After cases within the first 2 follow-up years were excluded, the 'ROM/CRP' pattern was no longer associated with CRC risk, suggesting potential influence of preclinical disease on these associations. By application of PCA, the study identified 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' as biomarker patterns representing potentially important pathways for CRC development.

引用

页码：261 / 275

页数：15

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