Colorectal Cancer Epigenetics: The Role of Environmental Factors and the Search for Molecular Biomarkers

Abstract

This review presents an evenhanded evaluation of the role of epigenetics in the development of colorectal cancer, and investigates the extent of environmental influences on modulating this disease. Advances in our understanding of chromatin structure, histone modification, transcriptional activity and DNA methylation have lead to an integrated approach to the role of epigenetics in carcinogenesis. Epigenetic mechanisms appear to permit response of individuals to environment through change in gene expression and are involved in inactivating one of the two X chromosomes in women. Epigenetic changes play an important role in development and can also arise stochastically as individuals age. Because epigenetic alterations are potentially reversible, thereby allowing malignant cells to revert to the normal state, there is potential to develop effective strategies to prevent or even reverse this curable cancer. Moreover, because the methylation status of a specific sequence or the pattern of methylation across the genome can now be measured accurately, molecular biomarkers of screening, diagnosis, prognosis, prediction of treatment and those related to risk assessment can be developed using sophisticated molecular genetic technologies. Although in many cases a high sensitivity and specificity of the detection assays has been achieved, there still remains ample room for improvement in areas of sample preparation, assay design and marker selection.

Key words:

• Aging
• Chromosome Inactivation
• CpG
• Gene Silencing
• Imprinting
• MSI
• Nutrition
• Polymorphism
• Pyrosequencing
• Therapy

I express my thanks to Dr. Yin-Tak Woo for his editorial help and careful review of the manuscript, and Dr. Ron R. Allison for his support.

Notes

∗Qualtitaive (COBRA or Southern method).

^#Quantitaive (MSP method).

⁺ND: not done.

∗Sensitive: detection of one methylated copy in 1000. N, no; Y, yes.

^•Quantitative: able to measure the amount of targeted analyte.

°Comethylation: detection of methylation only when simultaneously present in more than one CpG.

^◊High throughput.

∗Homogenous: assay is carried out in one tube to reduce potential contamination; N: no; Y: yes. Modified from (2).