학술논문

Identification of metabolites associated with prostate cancer risk: a nested case-control study with long follow-up in the Northern Sweden Health and Disease Study
Document Type
article
Source
BMC Medicine, Vol 18, Iss 1, Pp 1-14 (2020)
Subject
Prostate cancer
Metabolomics
Nested case-control study
Nuclear magnetic resonance spectroscopy
Mass spectrometry
Risk biomarkers
Medicine
Language
English
ISSN
1741-7015
Abstract
Abstract Background Prostate cancer is the second most frequently diagnosed cancer in men. Metabolomics can potentially provide new insights into the aetiology of prostate cancer by identifying new metabolic risk factors. This study investigated the prospective association between plasma metabolite concentrations and prostate cancer risk, both overall and by stratifying for disease aggressiveness and baseline age. Methods In a case-control study nested in the Northern Sweden Health and Disease Study, pre-diagnostic concentrations of 148 plasma metabolites were determined using targeted mass spectrometry- and nuclear magnetic resonance-based metabolomics in 777 prostate cancer cases (follow-up ≥ 5 years) and 777 matched controls. Associations between prostate cancer risk and metabolite concentrations were investigated using conditional logistic regression conditioned on matching factors (body mass index, age and sample storage time). Corrections for multiple testing were performed using false discovery rate (20%) and Bonferroni. Metabolomics analyses generated new hypotheses, which were investigated by leveraging food frequency questionnaires (FFQs) and oral glucose tolerance tests performed at baseline. Results After correcting for multiple testing, two lysophosphatidylcholines (LPCs) were positively associated with risk of overall prostate cancer (all ages and in older subjects). The strongest association was for LPC C17:0 in older subjects (OR = 2.08; 95% CI 1.45–2.98; p