Some cancers involve the inappropriate silencing or activation of genes through epigenetic changes - chemical modifications to DNA and proteins that control gene activity without causing a change in DNA sequence.
Though the epigenetic silencing of certain genes is critical throughout life, epigenetic information is less stable than the DNA sequence and may change over a lifetime. Some epigenetic changes can be modified by environmental factors, including drugs.
Epigenetic regulation of genes is essential for health, and flaws can lead to cancer and other diseases. But the flaws themselves could potentially be used to detect and even prevent tumors.
For example, the gene GSTP1 normally protects cells from damage by environmental toxins. But, in some prostate tumors, the gene is silenced by the addition of chemicals called methyl groups to DNA. Researchers at Johns Hopkins University developed an experimental screening test to detect this DNA methylation, the most common epigenetic change.
"Cancer epigenetics is important for prevention because we may be able to use methylation markers to identify people at higher risk of cancer and perhaps detect cancer earlier," said Dr. Mukesh Verma in NCI's Division of Cancer Control and Population Sciences (DCCPS) 1, one of several divisions conducting epigenetics research.
Investigators in DCP's Early Detection Research Network 2 are engaged in analytical validation of GSTP1 methylation for prostate cancer, as well as other genes linked to breast, kidney, and bladder cancers.
DCP has also led workshops and discussions on potential application of hypermethylation as a biomarker for early cancer detection, diagnosis, and prognosis. A recent workshop sponsored by the DCP Cancer Biomarkers Research Group 3 and the National Institute of Standards and Technology developed guidelines and recommendations for reagents, tools, and protocols for quantitative measurement of methylation in affected organ sites. A summary by Drs. Jacob Kagan and Sudhir Srivastava of DCP will be published soon in Cancer Research.
"We cannot reverse genetic mutations, but by using drugs we may be able to reverse changes in methylation," said Dr. Verma. "This approach has promise for prevention."
Diet also may affect methylation. Giving pregnant mice diets rich in methyl donors - including folic acid, choline, methionine, and genistein, an ingredient in soy - can modify the methylation patterns of a certain gene in their offspring. This can cause a change in coat color that may be associated with a reduced cancer risk.
"Epigenetic information presumably can be modified by environmental factors, including diet, and that's intriguing," said Dr. Sharon Ross of DCP. "We're getting closer to understanding how we might modify epigenetic changes associated with disease."
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