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Cancer Epidemiol Biomarkers Prev. 2019 Jan;28(1):99-109. doi: 10.1158/1055-9965.EPI-17-1017. Epub 2018 Oct 1.

Dietary Heterocyclic Amine Intake and Colorectal Adenoma Risk: A Systematic Review and Meta-analysis.

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Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich, Zurich, Switzerland.
Cancer Registry of the Cantons Zurich and Zug, Zurich, Switzerland.
Departamento de Medicina Legal y Toxicología, Facultad de Medicina de Granada, Universidad de Granada, Granada, Spain.
University Center of Health Sciences at Klinikum Augsburg (UNIKA-T), Ludwig-Maximilians University of Munich, Augsburg, Germany.
Helmholtz Zentrum München, Institute of Epidemiology, Neuherberg, Germany.
Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich, Zurich, Switzerland.



Heterocyclic amines (HCA) are potent carcinogenic substances formed in meat. Because of their mutagenic activity, they may increase the risk of colorectal adenomas, which are the precursors of colorectal cancer, one of the most prevalent cancers worldwide. The aim of this meta-analysis was to synthesize the knowledge about the intake of HCAs and its associations with CRA.


We conducted a systematic search in PubMed and EMBASE. We used odds ratios (OR); or relative risks, RR) from every reported intake and compared the highest versus lowest level of dietary HCAs. In addition, we assessed a dose-response relationship.


Twelve studies on HCA intake and risk of CRA were included in our analysis. We observed a statistically significant association when comparing top versus bottom intake category of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine [PhIP; OR = 1.20; 95% confidence interval (CI) = 1.12-1.29], 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx; OR = 1.20; 95% CI = 1.08-1.34), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx; OR = 1.16; 95% CI = 1.05-1.27), benzo(a)pyrene (BaP; OR = 1.15; 95% CI = 1.04-1.27), and mutagenicity index (OR = 1.22; 95% CI = 1.06-1.41). Furthermore, we observed a significant dose-response effect for PhIP, MeIQx, and mutagenicity index.


This meta-analysis suggests that there is a positive association of HCAs, BaP, mutagenicity index with risk of CRA. In addition, our dose-response analyses showed an increased risk of CRA for PhIP, MeIQx, and mutagenicity index.


This study provides evidence for a positive association between the dietary intake of meat mutagens and CRA risk.

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