Sáb. Nov 28th, 2020

Each person is born with a set of genes inherited and recombined into a unique blueprint or map. The expression of those genes is not just dependent on inheritance but how the genes interact with the outside environment (epigenetics). In other words, genes are not static. One can have oncogene mutations, but never develop cancer. In fact, 40% of people with BRCA positive gene mutations do not. Using genomic information to predict the development of a disease process such as cancer is tricky due to the complexity of our immune system.

However, we can use genomic data to look at factors affecting the ability of the body to:

  • Seek and find pre-cancerous and cancerous cells
  • Undergo apoptosis
  • Undergo DNA and cell cycle repair processes

Most conventional oncology genetic testing looks at specific oncogenes associated with cancer development such as the BRCA I and II mutations in breast and gynecological cancers, JAK2 mutations in myeloproliferative disorders, KRAS in pancreatic cancer, and APC in colon cancer. While these are important and specific treatment have been created accordingly, the power of a properly functioning immune system is often overlooked.

Data containing over 3,400 genes is readily available from 23 and Me, and Ancestry. Using complex, analytical software, such as OPUS23 which interfaces in real time to peer reviewed research, raw data can be assessed, and reports generated. Genes vital to processes that promote cancer prevention and remission can be analyzed for potential function and epigenetic affecters. This technology is being used to guide more personalized treatment plans for cancer patients. Resulting assessments provide information on the effects of environmental toxins, medication, supplements, nutrients from food, mind body therapies and general dietary recommendations for genes and mutations. Once suggestions are implemented, clinicians can monitor DNA oxidative damage, glutathione and Natural Killer Cell activity. We look for these values to improve as a result of specific changes to lifestyle, supplementation and diet.

Here are some examples to help with our understanding of how a report would be generated. Three of the most important genes clinicians assess in all cancer patients are interferon gamma, p53 and AKT. We’ll look at why they are important and how the data specifically relates to nutrients that might be recommended by a report. Comprehensive reports include other useful information as mentioned above.

Affecting the Body’s Immune Surveillance System: Natural Killer Cells and Interferon gamma

Natural Killer (NK) cells play an essential role in the surveillance of pre-cancerous and cancer cells. They act to phagocytose dysplastic cells and to produce cytokines which activate other cells, like

CD8 cells that further mount anti-tumor responses. Interferon gamma (IFN) is associated with anti proliferative, pro apoptotic and anti-tumor mechanisms. IFN is also associated with tumor surveillance by NK cells and downregulation of cell cycle checkpoint inhibitors. IFN mediated responses are positively associated with patient survival in several cancers.

Nutrient supporting proper INF gamma production and activity include: Theophylline found in cocoa beans, and black tea, Myrcene found in bay, and hops, Gingerol found in ginger, L-arginine found in sesame, wild rice, soybean, walnuts, chickpea, peanut, and mung beans, Cinnamon, and Beta cryptoxanthin which is found in Papaya, mango, peaches, oranges, tangerines, bell peppers, watermelon.

Safe-Guards to Damage: Apoptosis

There are several processes the body uses to prevent and correct damaged cells, damaged DNA, and damaged protein. One of these essential processes is called apoptosis. Apoptosis is defined as programmed cell death and occurs when a cell/DNA is damaged. It is an extremely important way of self-elimination for pre-cancerous cells and is highly regulated. There are genes that promote apoptosis like p53 and genes that suppress apoptosis like AKT, also known as survival factors. Proper functioning of apoptosis depends on genetic mutations, environmental factors, nutritional status and is affected by medications as well.

AKT1 (PI3K) – Alpha serine/threonine protein kinase is a survival factor which regulates apoptosis. It acts to turn off other proteins associated with proper apoptosis. Over activation (i.e. suppression of apoptosis) can over stimulate cells and result in abnormal cells proliferation = oncogenesis. Abnormalities are common in cancer: gastric, ovary, pancreatic, colorectal, breast and prostate. There are five alleles where mutations can occur. If mutations are significant enough, patients can have over or under activity.

This gene and its product, according to peer reviewed studies, can be affected by nutrition. Mutations resulting in over activity suppress apoptosis and may increase the risk of pre-cancerous and cancerous cells. In these circumstances, nutritional antagonists are appropriate. N-acetyl cysteine and theanine fall under this category. N-acetyl cysteine is found in Brussel sprouts, lentils, oatmeal, sunflower seeds, red peppers, garlic, onions. Theanine is found in green and black tea; nuts, seeds, beans, lentils, and soy/tempeh.

Surveillance of the Cell Cycle: p53

Most cells in our body undergo division process called mitosis. A cell grows, its DNA is exactly replicated in preparation for cellular division. What was once one cell, becomes two and the process starts again. I’ve used two sentences to describe cell division, but it is anything that simplistic. There is a massive amount of control and check points involved because one mistake can cause a normal cell to be converted to a pre-cancerous or cancer cell (aka immortal cells, aka undifferentiated cells). The cell cycle check points search for size, DNA replication, fidelity, nutrients, chromosome spindle attachment and DNA damage to name a few significant essential processed that must be executed correctly. If minor mistakes are made the cell does have the ability to correct them via repair enzymes or activation of a process called apoptosis (aka cell programmed death). Functioning of cell cycle surveillance for mistakes, repair enzymes, and apoptosis is vital to the prevention of cancer development.

All along the way nutrients from food and possibly supplements serve as coenzymes and cofactors to help this process run correctly. For example, magnesium is essential in DNA replication fidelity, Vitamin B12 is necessary for DNA replication and antioxidants such as Vitamin C and E are necessary for chromosomal damage. Deficiencies in vitamins and minerals can cause an increase in cell cycle mistakes.

P53 is a gene that produces a protein known as the guardian of the genome. It is the most common gene mutation found in about 50% of all cancers. P53 is a type of tumor suppressor gene that encodes for a protein that inhibits the development and growth of tumors. The main function is to repair DNA in order to prevent altered DNA. When the DNA damage is too extensive to be repaired, P53 protein signals cells to undergo apoptosis. Nutrients that act as agonists of P53 include lemons and those in the mint family.

I mentioned Myrcene above relating to agonistic activity on IFN gamma expression and Natural Killer cell activity. Myrcene is also found in Cannabis and is the most abundant monoterpene in the plant, therefore Cannabis is a great source of this component. Recall that IFN gamma is a cytokine that triggers a cellular response to viral, bacterial and parasitic infections, but also has important immunoregulatory functions. Its activation potentiates anti- tumor effect of cells including Natural Killer cells. This at a genetic level is of importance to cancer prevention.

In summary, genomic analysis can be a powerful tool in creating personalized diet and lifestyle plans in complementary cancer care. Raw data acquisition is relatively simple, and because of the availability of instruments like OPUS23 we can generate more accurate plans for our patients which can be measured with laboratory tests such as DNA oxidative damage, glutathione and Natural Killer cell profiles. I recommend that all cancer patients consider using these tools.

About OPUS23 software

Rather than just looking at the function of a handful of pre-determined SNPs without any associated research (and no way of knowing why the report chooses one form of the SNP to be listed as the risk over another form), Opus23 is a learning tool which allows the user multiple ways of visualizing the raw data of (currently) over 3,400 hand-curated SNPs by expert editors, most of which contain additional information and research by the editors about the SNP and gene, allowing the doctor to create user-defined reports tailored specifically to the patient’s presenting problems as well as creating custom templates for favorite scenarios or using templates produced by colleagues using the program. A multi-function cross-platform search enables the user to find relevance in complex algorithms, tissue-based activity of potentially compromised enzymes, protein-protein interactome, metabolic pathways with imputed gene function level, ClinVar and GWAS databases, all based on peer-reviewed studies and under constant editorial review. A tailored protocol can be curated for any of the current list of 3,426 genes influenced by 1,112 agents as reported in 2,192 hand-curated PubMed citations of interactions between genes and natural agents, classified by type of study (human, animal or in vitro). A new development which will be launched as soon as the labs make it available is the ability to upload other test data such as organic acid test results and view the interaction with the DNA raw data. This innovation, especially being linked to scientific studies is a powerful tool. 

Dr. Lisa A. Price, ND is a licensed clinician specializing in complementary cancer care and culinary nutrition, National Institute of Health Research Fellow, and author of three books (Demos Health Inc., and adjunct faculty at Bastyr University. She is a certified expert curator of OPUS23 software.

 

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