Metabolic pathways in sporadic colorectal carcinogenesis: A new proposal

Given the reports made about geographical differences in Colorectal Cancer (CRC) occurrence, suggesting a link between dietary habits, genes and cancer risk, we hypothesise that there are four fundamental metabolic pathways involved in diet-genes interactions, directly implicated in colorectal carcinogenesis: folate metabolism; lipid metabolism; oxidative stress response; and inflammatory response. Supporting this hypothesis are the ev-idence given by the significant associations between several diet-genes polymorphisms and CRC, namely: MTHFR, MTR, MTRR and TS (involved in folate metabolism); NPY, APOA1, APOB, APOC3, APOE, CETP, LPL and PON1 (involved in lipid metabolism); MNSOD, SOD3, CAT, GSTP1, GSTT1 and GSTM1 (involved in oxidative stress response); and IL-1, IL-6, TNF-?, and TGF-? (involved in inflammatory response). We also highlight the association between some foods/nutrients/nutraceuticals that are important in CRC prevention or treatment and the four metabolic pathways proposed, and the recent results of genome-wide association studies, both assisting our hypothesis. Finally, we propose a new line of investigation with larger studies, using accurate dietary bio-markers and investigating the four metabolic pathways genes simultaneously. This line of investigation will be essential to understand the full complexity of the association between nature and nurture in CRC and perhaps in other types of cancers. Only with this in-depth knowledge will it be possible to make personalised nutrition recommendations for disease prevention and management.

Automated summary

This study discusses the link between dietary habits, genes, and colorectal cancer occurrence, proposing four fundamental metabolic pathways and analyzing related gene polymorphisms. It also highlights the association between diet and genes, as well as the importance in CRC prevention or treatment.