Pre-diagnostic metabolite concentrations and prostate cancer risk in 1077 cases and 1077 matched controls in the European Prospective Investigation into Cancer and Nutrition

被引：50

作者：

Schmidt, Julie A. ^{[1
]}

Fensom, Georgina K. ^{[1
]}

Rinaldi, Sabina ^{[2
]}

Scalbert, Augustin ^{[2
]}

Appleby, Paul N. ^{[1
]}

Achaintre, David ^{[2
]}

Gicquiau, Audrey ^{[2
]}

Gunter, Marc J. ^{[2
,3
]}

Ferrari, Pietro ^{[2
]}

Kaaks, Rudolf ^{[4
]}

Kuehn, Tilman ^{[4
]}

Floegel, Anna ^{[5
]}

Boeing, Heiner ^{[5
]}

Trichopoulou, Antonia ^{[6
,7
]}

Lagiou, Pagona ^{[6
,7
,8
]}

Anifantis, Eleutherios ^{[6
]}

Agnoli, Claudia ^{[9
]}

Palli, Domenico ^{[10
]}

Trevisan, Morena ^{[11
,12
]}

Tumino, Rosario ^{[13
]}

Bueno-de-Mesquita, H. Bas ^{[14
]}

Agudo, Antonio ^{[15
]}

Larranaga, Nerea ^{[16
,17
]}

Redondo-Sanchez, Daniel ^{[17
,18
]}

Barricarte, Aurelio ^{[17
,19
,20
]}

Maria Huerta, Jose ^{[17
,21
]}

Quiros, J. Ramon ^{[22
]}

Wareham, Nick ^{[23
]}

Khaw, Kay-Tee ^{[24
]}

Perez-Cornago, Aurora ^{[1
]}

Johansson, Mattias ^{[2
]}

Cross, Amanda J. ^{[3
]}

Tsilidis, Konstantinos K. ^{[3
,25
]}

Riboli, Elio ^{[3
]}

Key, Timothy J. ^{[1
]}

Travis, Ruth C. ^{[1
]}

机构：

[1] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford OX3 7LF, England

[2] Int Agcy Res Canc, F-69372 Lyon 08, France

[3] Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London W2 1PG, England

[4] German Canc Res Ctr, Fdn Publ Law, Div Canc Epidemiol, DE-69120 Heidelberg, Germany

[5] German Inst Human Nutr DIfE Potsdam Rehbrucke, Dept Epidemiol, DE-14558 Nuthetal, Germany

[6] Hellen Hlth Fdn, GR-11527 Athens, Greece

[7] Univ Athens, Collaborating Ctr Nutr & Hlth, Dept Hyg Epidemiol & Med Stat,Sch Med, Unit Nutr Epidemiol & Nutr Publ Hlth,WHO, GR-11527 Athens, Greece

[8] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[9] Fdn IRCCS Ist Nazl Tumori, Epidemiol & Prevent Unit, Via Venezian 1, I-20133 Milan, Italy

[10] Canc Res & Prevent Inst ISPO, Canc Risk Factors & Life Style Epidemiol Unit, I-50134 Florence, Italy

[11] Univ Turin, Dept Med Sci, Canc Epidemiol Unit CERMS, I-10126 Turin, Italy

[12] CPO Piemonte, I-10126 Turin, Italy

[13] Civ MP Arezzo Hosp, Canc Registry & Histopathol Unit, I-97100 Asp, Ragusa, Italy

[14] Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis DCD, NL-3720 BA Bilthoven, Netherlands

[15] Catalan Inst Oncol IDIBELL, Canc Epidemiol Res Program, Unit Nutr & Canc, Barcelona 08908, Spain

[16] Reg Govt Basque Country, Publ Hlth Div Gipuzkoa, Donostia San Sebastian 20014, Spain

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

[18] Univ Granada, Hosp Univ Granada, Inst Invest Biosanitaria Ibs GRANADA, Escuela Andaluza Salud Publ, Granada 18012, Spain

[19] Navarra Publ Hlth Inst, Pamplona 31003, Spain

[20] Navarra Inst Hlth Res IdiSNA Pamplona, Pamplona, Spain

[21] IMIB Arrixaca, Dept Epidemiol, Murcia Reg Hlth Council, Murcia 30003, Spain

[22] Publ Hlth Directorate, Asturias 33006, Spain

[23] Univ Cambridge, MRC, Epidemiol Unit, Cambridge CB2 0SR, England

[24] Univ Cambridge, Sch Clin Med, Cambridge CB2 2QQ, England

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

来源：

BMC MEDICINE | 2017年 / 15卷

基金：

英国医学研究理事会;

关键词：

Acylcarnitines; Amino acids; Biogenic amines; European Prospective Investigation into Cancer and Nutrition (EPIC); Glycerophospholipids; Hexose; Mass spectrometry; Metabolomics; Prospective study; Prostate cancer risk; Sphingolipids; METABOLOMICS; VARIABILITY; PLASMA; PHOSPHATIDYLCHOLINE; REPRODUCIBILITY; PROLIFERATION; SPHINGOMYELIN; PREVENTION; CARCINOMA; PROFILES;

D O I：

10.1186/s12916-017-0885-6

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Little is known about how pre-diagnostic metabolites in blood relate to risk of prostate cancer. We aimed to investigate the prospective association between plasma metabolite concentrations and risk of prostate cancer overall, and by time to diagnosis and tumour characteristics, and risk of death from prostate cancer. Methods: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition, pre-diagnostic plasma concentrations of 122 metabolites (including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose and sphingolipids) were measured using targeted mass spectrometry (AbsoluteIDQ p180 Kit) and compared between 1077 prostate cancer cases and 1077 matched controls. Risk of prostate cancer associated with metabolite concentrations was estimated by multi-variable conditional logistic regression, and multiple testing was accounted for by using a false discovery rate controlling procedure. (Continued on next page) Results: Seven metabolite concentrations, i.e. acylcarnitine C18: 1, amino acids citrulline and trans-4-hydroxyproline, glycerophospholipids PC aa C28: 1, PC ae C30: 0 and PC ae C30: 2, and sphingolipid SM (OH) C14: 1, were associated with prostate cancer (p < 0.05), but none of the associations were statistically significant after controlling for multiple testing. Citrulline was associated with a decreased risk of prostate cancer (odds ratio (OR1SD) = 0.73; 95% confidence interval (CI) 0.62-0.86; ptrend = 0.0002) in the first 5 years of follow-up after taking multiple testing into account, but not after longer follow-up; results for other metabolites did not vary by time to diagnosis. After controlling for multiple testing, 12 glycerophospholipids were inversely associated with advanced stage disease, with risk reduction up to 46% per standard deviation increase in concentration (OR1SD = 0.54; 95% CI 0.40-0.72; ptrend = 0.00004 for PC aa C40: 3). Death from prostate cancer was associated with higher concentrations of acylcarnitine C3, amino acids methionine and trans-4-hydroxyproline, biogenic amine ADMA, hexose and sphingolipid SM (OH) C14: 1 and lower concentration of glycerophospholipid PC aa C42: 4. Conclusions: Several metabolites, i.e. C18:1, citrulline, trans-4-hydroxyproline, three glycerophospholipids and SM (OH) C14:1, might be related to prostate cancer. Analyses by time to diagnosis indicated that citrulline may be a marker of subclinical prostate cancer, while other metabolites might be related to aetiology. Several glycerophospholipids were inversely related to advanced stage disease. More prospective data are needed to confirm these associations.

引用

页数：14

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