Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Jun 24, 2021; 12(6): 482-499
Published online Jun 24, 2021. doi: 10.5306/wjco.v12.i6.482
Phytochemically rich dietary components and the risk of colorectal cancer: A systematic review and meta-analysis of observational studies
Pia Borgas, Guadalupe Gonzalez, Kirill Veselkov, Reza Mirnezami
Pia Borgas, Faculty of Medical Sciences, University College London, London WC1E 6BT, United Kingdom
Guadalupe Gonzalez, Department of Computing, Imperial College London, London SW7 2RH, United Kingdom
Kirill Veselkov, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London SW7 2AZ, United Kingdom
Reza Mirnezami, Department of Colorectal Surgery, Royal Free Hospital, London NW3 2QG, United Kingdom
Author contributions: Borgas P performed the literature searching, study identification, data analysis and manuscript preparation; Gonzalez G performed data analysis and manuscript preparation; Veselkov K performed study inception, data analysis and manuscript preparation; Mirnezami R performed study inception, study identification, literature searching, data analysis and manuscript preparation; all authors have read and approved the final manuscript.
Conflict-of-interest statement: The authors declare no conflicts interests.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Reza Mirnezami, FRCS, MBBS, PhD, Senior Lecturer, Surgeon, Department of Colorectal Surgery, Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, United Kingdom.
Received: February 9, 2021
Peer-review started: February 9, 2021
First decision: March 31, 2021
Revised: April 6, 2021
Accepted: June 2, 2021
Article in press: June 2, 2021
Published online: June 24, 2021
Research background

Personalized nutrition and protective diets and lifestyles represent a key cancer research priority according to The Third Expert Report from the World Cancer Research Fund (2018) and the recently published National Institute of Health strategic plan. The association between consumption of specific dietary components and colorectal cancer (CRC) incidence has been evaluated by a number of large-scale, population-based, epidemiological studies, which have identified certain food items as having protective potential, though the findings have been inconsistent.

Research motivation

Although previous meta-analyses have sought to evaluate the impact of some of these food items, results have been contradictory and inconclusive. To date there has been no comprehensive meta-analysis, including more recent multinational cohort studies, which unifies all five of these food items, assessing all available and recent evidence. Furthermore, anticancer properties could be explained by genomic effects of certain compounds contained in these phytochemically rich foods. This may help explain the underlying cause for any protective associations. Thus, we present a systematic review and meta-analysis on the potential protective role of five common phytochemically rich dietary components (nuts, cruciferous vegetables, citrus fruits, garlic and tomatoes) in reducing CRC risk. Putative anticarcinogenic mechanisms are highlighted through gene-set enrichment analysis.

Research objectives

To investigate the independent impact of increased intake of five dietary constituents (nuts, cruciferous vegetables, citrus fruits, garlic and tomatoes) on CRC risk in the general population.

Research methods

Medline and Embase were systematically searched, from time of database inception to January 31, 2020, for observational studies reporting CRC incidence relative to intake of one or more of nuts, cruciferous vegetables, citrus fruits, garlic and/or tomatoes in the general population. Data were extracted by two independent reviewers and analyzed in accordance with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) reporting guidelines and according to predefined inclusion/exclusion criteria. Effect sizes of studies were pooled using a random-effects model. Using gene set enrichment analysis, a profile of genomic perturbations caused by each food item was built and biological pathways affected by these perturbations were identified.

Research results

This systematic review and meta-analysis of 46 observational studies found that increased dietary consumption of cruciferous vegetables, citrus fruits, garlic and tomatoes is associated with a significant reduction in the risk of developing CRC. Consumption of nuts exhibited a similar trend, but results were not significant. The underlying mechanisms of the observed effects remain unclear, although putative anticarcinogenic mechanisms are proposed using the results of gene-set enrichment analysis of gene-protein perturbations caused by active compounds within each food item.

Research conclusions

Increased cruciferous vegetable, garlic, citrus fruit and tomato consumption are all inversely associated with CRC risk. These findings highlight the potential for precision nutrition strategies and development of personalized food maps in CRC prevention for both the general population and at-risk individuals.

Research perspectives

The findings should stimulate future research to focus on understanding the nature of the observed effects, by exploring the epigenetic interactions of active compounds within the investigated foods. Additionally, linear and continuous exposure analyses should be explored to identify consumption thresholds for the observed effects. Results should then encourage the design of randomized controlled trials to assess food-based approached in modifying CRC risk.