Introduction Colorectal cancer (CRC) is the 3rd most common cancer in the UK. There is a lack of robust biomarkers of CRC risk which could act as surrogate endpoints for studies investigating modifiers of CRC risk. Epigenetic changes (aberrant DNA methylation marks) in the WNT-related Secreted Frizzled Related Protein 4 (SFRP4), a gene whose expression is down-regulated early in CRC development, may be a potential biomarker of CRC risk. Such epigenetic changes occur early in tumorigenesis and may contribute causally to CRC progression. In addition, they may respond to diet and other lifestyle determinants of CRC risk.
Methods DNA was extracted from macroscopically normal mucosal biopsies from the rectum of volunteers at a relatively lower (healthy volunteers) and higher (patients with adenomatous polyps) CRC risk in the BORICC Study. Methylation of SFRP4 was quantified by Pyrosequencing and data were analysed by analysis of variance.
Results SFRP4 promoter methylation was quantified in 253 biopsies from lower and 96 biopsies from higher CRC risk participants. Methylation of the SFRP4 promoter was significantly (p=0.001) greater in biopsies from those at higher CRC risk. In addition, increasing age (a strong modulator of CRC risk) was significantly (p<0.001) associated with increased SFRP4 methylation.
Conclusion This study showed that SFRP4 methylation is significantly greater in macroscopically normal rectal biopsies from those at higher CRC risk. This aberrant epigenetic mark may be causal for CRC risk and further studies are needed to investigate whether methylation of SFRP4 is reversible by dietary and other interventions.
Competing interests None declared.