Meta-analysis of homocysteine-related factors on the risk of colorectal cancer.

Chong Ho Yu,S Pamela K Shiao,Amanda Lie

doi:10.18632/oncotarget.25355

Chong Ho Yu, S Pamela K Shiao + Show 1 more

Open Access

https://doi.org/10.18632/oncotarget.25355

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Abstract

The major objective of this meta-analysis was to examine the association between homocysteine and related measurements with the risk of colorectal cancer (CRC) and adenomatous polyps (AP). Many studies presented an association between methyltetrahydrofolate reductase (MTHFR) gene polymorphisms and risk of CRC. Yet, there have been variances on what homocysteine-related and dietary factors play on the risk of CRC or AP, in association with folate-related one carbon metabolism pathways. We pooled analyses to examine comprehensively all homocysteine related factors including blood tests measurements, dietary, and lifestyle factors for their associations with the risk of CRC and AP. We located 86 articles published from 1995 to 2017. The results revealed that elevated homocysteine levels and decreased vitamin B12 levels in the blood were associated with increased risks of CRC and AP, with case-control studies having greater significant effect sizes compared to that of cohort-control studies. Decreased methionine and vitamin B6 levels in the blood increased the risk of CRC. MTHFR 677 TT and CT polymorphisms were interacting with elevated homocysteine levels to increase the risk of CRC. Decreased dietary fiber, methionine, vitamin B9 or folate, and vitamin B6 intakes were associated with increased risks of CRC; whereas, increased dietary B12 intake, alcohol intake, and smoking were associated with increased risk of CRC. Further studies can be conducted to examine the mechanistic differences of blood levels of homocysteine-related and dietary factors, including different types of dietary fiber, for their effects on decreasing the homocysteine toxicity to prevent CRC.

Highlights

Colorectal cancer (CRC) is the third most common cancer diagnosed in the United States, and the third leading cause of cancer-related deaths in both men and women [1, 2]
A total of 86 articles were identified between the years of 1995 to 2017; according to colon health-disease types, 63 papers focused on colorectal cancer (CRC) only, 5 papers reported on both CRC and adenomatous polyps (AP), and 18 papers reported with AP cases only
There is no significance in cases (CRC or AP) compared to control for smoking status across ethnic subgroups in the cohort studies (Supplementary Table 4B). In this meta-analysis, we investigated homocysteinerelated blood test measurements, and dietary and lifestyle factors involved in the one carbon metabolism (OCM) pathway for the risk of CRC

Summary

Introduction

Colorectal cancer (CRC) is the third most common cancer diagnosed in the United States, and the third leading cause of cancer-related deaths in both men and women [1, 2]. Elevated homocysteine level is an independent predictor for all-cause mortality [11,12] and it compromises health of all organ systems [13,14,15,16], affecting epigenetic changes for DNA synthesis and healthy living. When gene mutations in the OCM pathway occur, such as with the methylenetetra-hydrofolate reductase (MTHFR) C677T (rs 1801133) polymorphism, there is a deficiency in the methyl-folate enzyme and the activity in the OCM pathway is impaired [8, 9, 16,17,18]. MTHFR and other genes in the OCM pathway play important roles in DNA methylation, a key mechanism in epigenetics, and nutrigenomics within the OCM pathway [6,7,8]. An increase in methyl donors such as vitamin B2, B6, B9, B12, or methionine, may help compensate the deficiency of the enzymes in OCM pathways during DNA methylation, synthesis and repair, preventing carcinogenesis [19, 20]

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