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Epigenetics and the Epidemology of Cancer

From the April 15 blog entry:

"So I think the topic of Epigenetics has a bearing on (the epidemiology of) childhood cancer.
And the fact that you can pass on an environment conducive to mutations without being the origin of the mutation. Theoretically the parents or the grandparents could be the origin of the "presentation" of the genes without actually passing on mutated genes (#2).

Epigenetics deals with the presentation of genes - which (epigenetic) structure is "heritable" from generation to generation even IF there are no (genetic) mutations. That means toxicity from an earlier exposure can "degrade" the epigenetic status - resulting in a "signaling environment" that is conducive to the survival of mutations. Mutations that can themselves direct further epigenetic "modifications" to support their own survival (a downward spiral of malignancy) (#3).

So the maligancy of cancer is directly related to supporting genetic AND epigenetic problems. For example - mutations could normally be trying to shut down the cells (apoptosis) but because of epigenetic issues, the cells refuse to listen. Also - mutations could be driving growth - but because of epigenetic issues, the cells refuse to differentiate.

The key word relating Epigenetics to the topic (Epidemiology of Cancer), I think, is "heritable". Heritable from earlier to later life. And also theoretically heritable from parents to children. In other words even if teenage smokers avoided cancer, they could still pass on poor epigenetic structure to their children ...that would increase the risk of mutations surviving and becoming malignant.

Could that mean cancer risk would grow over multiple generations of poor diet / toxic environment? I think so.

The good news is, that with nutritional epigenetic therapy (things like Green Tea (#5), Curcumin (#7), Quercetin (#8), etc.) the cellular signaling environment that supported the genetic mutations can be adjusted, supporting normal apoptosis (programmed cell death) and/or differentation, and also sensitising the cells to chemo, radiation, and/or immunology."

#1 http://www.ncbi.nlm.nih.gov/pubmed/18199978
Nutritional genomic approaches to cancer prevention research. (National Cancer Institute, Bethesda, MD)
#2 http://www.ncbi.nlm.nih.gov/pubmed/16503131
Histone modifications: signalling receptors and potential elements of a heritable epigenetic code. (University of Birmingham, UK)
#3 http://www.ncbi.nlm.nih.gov/pubmed/16491070
Epigenetic gene silencing in cancer - a mechanism for early oncogenic pathway addiction? (Johns Hopkins, Baltimore MD)
#4 http://www.ncbi.nlm.nih.gov/pubmed/16563357
Molecular targets of dietary agents for prevention and therapy of cancer. (M.D. Anderson, Houston, TX)
#5 http://www.ncbi.nlm.nih.gov/pubmed/17570133
Epigenetic and genetic mechanisms contribute to telomerase inhibition by EGCG. (U. of Alabama, Birmingham, AL)
#6 http://www.ncbi.nlm.nih.gov/pubmed/18271058
Chemical regulation of epigenetic modifications: opportunities for new cancer therapy. (Georgia State University, Atlanta, Georgia)
#7 http://www.nature.com/bjc/journal/v94/n2/abs/6602918a.html
Epigenetics provides a new generation of oncogenes and tumour-suppressor genes (Spanish National Cancer Center, Madrid)
#8 http://bloodjournal.hematologylibrary.org/cgi/content/abstract/109/8/3462
Epigenetic regulation of Wnt-signaling pathway in acute lymphoblastic leukemia ( University of Navarra, Pamplona, Spain)
#9 http://www.ncbi.nlm.nih.gov/pubmed/18692688
Epigenetics in acute myeloid leukemia (German Cancer Research Center, Heidelberg, Germany)
#10 http://www.ncbi.nlm.nih.gov/pubmed/18206229
Epigenetic-based treatments emphasize the biologic differences of core-binding factor acute myeloid leukemias
(Universitat Autonoma de Barcelona, Spain)

This is an encouraging field because it sets scientific teeth on the argument
...that there are common sense dietary things you can do to guard against cancer.

And that's not the ranting of some "wacko-health-nuts". See study above (#4).
That's M.D. Anderson Cancer Center Research Laboratory, Houston, Texas.