Relationships between adherence to the Mediterranean diet and methylation of WNT pathway-related genes implicated in colorectal cancer

Abstract

Introduction: Colorectal cancer (CRC) is strongly influenced by environmental factors including diet. Mediterranean diet (MD) adherence is associated with a lower incidence of all-cause mortality and an inverse association with CRC risk has been reported. WNT signalling is hyperactive in up to 85% of sporadic CRC because of abnormal methylation and expression of WNT pathway genes. Altered WNT signalling is a potential mechanism for the effects of diet on CRC risk. In this project the relationships between MD adherence and methylation of WNT pathway genes implicated in CRC are investigated. Methods: A literature search identified genes (WNT5A, WNT6 and WNT10A) associated with MD and CRC. DNA was extracted from rectal biopsies of BFU Study participants, bisulphite-modified, and PCR-amplified to identify DNA methylation at specific CpG sites by pyrosequencing. The MD score (MDS) was calculated from habitual dietary intake data. Participants were divided into two categories by dichotomising their MDS at the median. Results and conclusion: 40 participants were included in the study (age range 49-79 years). MDS ranged from 2-7 and participants. No significant relationships were observed between MD adherence and WNT5A, or WNT10A methylation (P>0.05). However, CpG site 5 within WNT6, was positively correlated with MDS (P=0.016). A post hoc analysis showed that methylation of WNT5A of polyp participants was lower in those with lower MDS compared to those with higher MDS.