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

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.