September 2016
By Ben Best
Most forms of cancer are almost entirely preventable. No more than 10% of cancer cases can be attributed to inherited genetic factors, while 90%-95% are caused by lifestyle and environmental factors.1
Tobacco alone accounts for 25%-30% of cancer deaths, diet for 30%-35%, infections for 15%-20%, and radiation (including ultraviolet light) up to 10%.1 Being overweight or obese is estimated to cause 4%-20% of cancer deaths.2 All of these factors create or lead to chronic inflammation,3 the most common cause of cancer.1,4
Cells in body tissues are normally “good citizens” that cooperate with other cells to facilitate body function. Cancer cells, by contrast, have no purpose other than to grow and multiply, contributing nothing to body function.
Many cancers are based on abnormal DNA or chromosomes, usually due to lifestyle or environmental DNA damage, but some are the result of inherited mutations.5 For example, although mutations in the BRCA1 gene are not common for the general population,6,7 for those having it, the risk of breast or ovarian cancer before the age of 70 is 65% or 39%, respectively.8 (It’s possible that lifestyle differences have some bearing on which BRCA1 carriers do or do not get cancer, but this has not been well studied.)
The two broad classes of genetic defects underlying cancer are (1) overactive oncogenes (genes that accelerate growth and multiplication), and (2) inactivated tumor suppressor genes (genes that normally prevent cancer).
Two of the most common oncogenes are PIK3CA (which promotes cell growth, survival, and motility)9 andKRAS (which greatly increases cell glucose uptake).10 The most common tumor suppressor gene is p53(which causes cells with defective DNA to self-destruct or stop replicating).11
Cancer begins with gene mutations that increase abnormal growth and replication. Factors that assist these processes enable cancer cells to immortalize, or promote the formation of new blood vessels to nourish the tumor. In more advanced stages, mutations allow cancer to spread to other organs, a process called metastasis. More than 90% of cancer deaths are due to metastasis.12 To reach the metastatic stage typically requires at least several mutations.13 The risk of cancer before age 40 is only about 2%, but by age 80 the risk increases to 50%.14
In the United States, the six most frequently diagnosed cancers are, in decreasing order: breast, lung, prostate, colorectal, bladder, and skin. The six most common causes of cancer death in the United States are, in decreasing order: lung, colorectal, pancreas, breast, prostate, and liver.15 Thanks to aggressive efforts to detect breast and prostate cancer in early stages, they are often cured. Pancreatic cancer, by contrast, is usually only detected in more advanced stages.
Normal cells generate most of their energy from glucose and oxygen in the mitochondria. Cancer cells, however, obtain their energy by glucose metabolism outside the mitochondria through glycolysis. Although it is 18 times more efficient to derive energy from glucose in mitochondria,16 cancer cells compensate by absorbing massive amounts of glucose, with rates of glycolysis up to 200 times greater than normal cells.17
Cancer cells use glucose primarily as a source of material for building cellular components, rather than for energy.17,18 High glucose utilization is so characteristic of cancer that cancer imaging with PET scans is based on detection of high glucose utilization.19
Dichloroacetate (DCA), a non-patented compound, counteracts a protective mechanism used by cancer cells that prevents glucose products from entering mitochondria, which would send the mitochondria into overdrive, resulting in cell death.18 Life Extension Foundation® is funding clinical trials to treat cancer patients with DCA.
With this background, let’s review the American Association for Cancer Research annual meeting, which was held April 18-22, 2015, in Philadelphia.
Colorectal Cancer
Grivennikov
Sergei Grivennikov, PhD, assistant professor, Fox Chase Cancer Center, Philadelphia, is a specialist in cancers of the large intestine and rectum. He provided insights on the most frequently mutated gene in colorectal cancer, the adenomatous polyposis coli (APC) gene. This defect is seen in 75% of sporadic colorectal cancers, but is due to an inherited mutation in less than 1% of cases.20
Chronic inflammation, characterized by the release of inflammatory cytokines (proteins) and DNA-damaging oxidants is typically the cause of colorectal gene mutations. Chronic inflammation not only contributes to the initiation of cancer mutations, but to tumor growth and metastasis.12 Inflammation leads to infiltration of bacteria into tumors, which enhances the inflammation by releasing endotoxins.21-23 A high-fat diet can result in excessive pro-inflammatory bile acids, which can increase cancer-causing bacteria.24 Calcium can help remove toxic bile acids.25,26
Trinchieri
Giorgio Trinchieri, MD, director for the Cancer and Inflammation Program, National Cancer Institute, Bethesda, Maryland, is concerned with the fact that inflammation contributes to abnormal bacteria in the gut, and that the abnormal bacteria interfere with anticancer chemotherapy.27 Dr. Trinchieri would like to alter the gut microbiota to improve cancer treatment.28 He recommends the use of probiotics, prebiotics, and transplantation of feces from healthy persons into cancer patients.29 The FDA has been blocking fecal transfer by insisting that human stools are a drug which will require FDA approval before it can be given to patients.30
Jobin
Christian Jobin, PhD, professor of medicine, University of Florida, Gainesville, is concerned with how inflammation induces colorectal cancer. Death from colorectal cancer is at least twice as high in persons with ulcerative colitis or Crohn’s Disease as for the general population.31 Dr. Jobin suggests that inflammation encourages expansion of gut microorganisms that can induce cancer,32 including more toxic strains of E. coli bacteria.33 Even without increasing the number of E. coli, inflammation can increase the propensity of E. coli to induce colorectal cancer.34 Dr. Jobin wants to develop bacteria-killing viruses that are specific for the toxic strains of E. coli most responsible for inflammation and cancer.
Aspirin against Colorectal Cancer
Andrew Chan, MD, program director, Gastroenterology, Massachusetts General Hospital, Boston, has investigated the use of aspirin to prevent colorectal cancer and to improve survival in colorectal cancer patients. Dr. Chan found that women who took the largest amounts of aspirin (325 mg more than 14 times per week) had the greatest (53%) reduction in risk of colorectal cancer.35 But he also found that those women had the highest risk of gastrointestinal bleeding.36 Dr. Chan discovered that aspirin increased survival in colorectal cancer patients with a PIK3CA mutation, but not in patients lacking this mutation.37 Dr. Chan has done genetic screening to better identify colorectal cancer patients who would or would not benefit from aspirin.38 Editor’s note: Studies using lower dose aspirin reduce cancer risk, but not as effectively (by 53%) as reported by Dr. Chan.98,99
Cervical Cancer
Douglas Lowy, MD, acting director, National Cancer Institute, Bethesda, Maryland, works on vaccination against human papillomavirus (HPV). HPV is nearly always the cause of cervical cancer,39 which is the second most common cause of cancer in women worldwide.40 HPV is almost twice as common in less developed countries compared to developed countries,41 and is the most common sexually transmitted infection, although symptoms are not usually manifest.42 A school HPV vaccination program for girls aged 12-17 was introduced in Australia in 2007. Prevalence of the types of HPV vaccinated against dropped to less than a quarter of the initial value in young women by 2011,43 and genital warts among women under 21 dropped from over 11% to less than 1%.44 DNA testing for HPV provides 60%- 70% better screening than Pap smears.45
The PIK3CA Oncogene Mutation
Vanhaesebroeck
Bart Vanhaesebroeck, PhD, professor, University College London Cancer Institute, London, England, is interested in the PIK3CA subset of PI3K ( PhosphoInositide 3-kinase) as one of the most frequently mutated genes in cancer, occurring in up to 40% of breast cancer cases, more than a third of cancers of the uterus, up to a third of colon cancers, and about a quarter of stomach cancers (among other cancers).46These mutations in PIK3CA result in excessive cell growth, multiplication, metastasis, and inhibition of apoptosis (cell suicide).9 PIK3CA mutations are one of the most common oncogene mutations in breast cancer (especially cases associated with increased estrogen response).47 PIK3CA-inhibiting substances can not only reduce PIK3CA activity,48 but normalize blood vessels, thereby facilitating delivery of other chemotherapeutic agents.49
Cancer Stem Cells
Kolev
Vihren Kolev, PhD, senior scientist, Verastem, Inc., Cambridge, Massachusetts, is attempting to eliminate cancer by targeting cancer stem cells. These cells are hard to eliminate. Often, apparently successful eradication of tumors by chemotherapy ultimately ends in failure because surviving cancer stem cells create a new, more resistant tumor. He described markers of cancer stem cells, such as focal adhesion kinase50 and aldehyde dehydrogenase 1,51,52 which have the possibility of making stem cells easier to locate and identify, and thus eliminate.
SIRT6 Protects Against Cancer
Mostoslavsky
Raul Mostoslavsky, MD, PhD, associate professor of Medicine, Harvard Medical School, is an expert in sirtuin proteins,53 the most well-known of which is SIRT1. SIRT1 extends the lifespan of yeast, worms, and flies when stimulated by resveratrol.54 Dr. Mostoslavsky, however, is most interested in the effect of SIRT6 on cancer. SIRT6 is localized at the telomeres at the end of chromosomes. It helps to maintain genetic stability, and prevents cellular aging.55 Dr. Mostoslavsky has demonstrated that SIRT6 maintains genetic stability by assisting with repair of damaged DNA.56 Cancer cells are greatly dependent on glycolysis to support rapid growth and multiplication. Dr. Mostoslavsky has shown that SIRT6 opposes this process, that reduction of SIRT6 fosters glycolysis, and that many cancers repress SIRT6.57 Life Extension Foundation is funding Dr. Vera Gorbunova to find SIRT6-activating therapies.
Enhancing the Immune System against Cancer
Schumacher
Ton Schumacher, PhD, professor, Netherlands Cancer Institute, Amsterdam, Netherlands, works on using the immune system to fight cancer. The role of the immune system in preventing cancer is apparent from the fact that AIDS victims and transplant recipients taking immune suppressant drugs have an increased risk of cancer.58,59 Cancer cells are able to evade or suppress the immune system. The journal Science called cancer immunotherapy the “breakthrough of the year” in 2013 because of the discovery of ways to prevent cancer from blocking the immune system.60 Cancer that has spread from its tissue of origin (metastatic cancer) is generally incurable. Metastatic melanoma has shown rapid tumor regression in nearly a third of patients receiving these kinds of immunotherapies (checkpoint inhibitors) that prevent cancer from blocking the immune system.60 Dr. Schumacher was part of a team that analyzed nearly five million mutations in over 7,000 cancers. Melanoma and lung cancer were found to have the highest frequency of mutations.61 Cancer cells that have the highest number of mutations, such as melanoma, are the most vulnerable to this type of (checkpoint inhibitor) immunotherapy.62
CRISPR Gene Editing to Fight Cancer
Tyler Jacks, PhD, director, Koch Institute for Integrative Cancer Research, Cambridge, Massachusetts, has been using the new CRISPR/Cas9 technology, which was developed for editing the human genome in 2013.63,64 CRISPR/Cas9 is based on a system used by bacteria to defend themselves against viruses. When bacteria are invaded by viruses, the bacteria store part of the virus’s DNA in the genome of their cell, called CRISPR. RNA copied from the CRISPR is attached to a Cas9 cutting enzyme. The RNA then guides the Cas9 enzyme to the virus to cut (and thereby destroy) the virus. CRISPR/Cas9 has been applied to gene editing by designing guide RNAs for specific DNA locations to be edited.63
Dr. Jacks has worked on a team that used CRISPR/Cas9 to cure an inherited disease in a mouse.65 He has also used CRISPR/Cas9 to create a mouse model of cancer.66 Such models can be used to study the features of many cancer types, and to experiment with potential therapies. Cancer cells can have a high mutation rate, although only a few of the mutations are thought to drive the cancer. CRISPR/Cas9 can be used to distinguish between mutations that drive cancer and mutations which do not. Dr. Jacks anticipates that CRISPR/Cas9 will be used to design immune system cells that target specific cancers.67
Conclusions/Interpretations
It is an unfortunate fact that almost all of modern medicine is based on treatment of disease, rather than on prevention, most tragically exemplified by cancer, which is so highly preventable. The key to prevention is better lifestyle. Unconventional health practices have the potential to reduce cancer incidence even more than the lifestyle changes advocated by conventional medicine. As I wrote in the December 2015 issue of Life Extension Magazine®, a low carbohydrate ketogenic diet can provide energy while depriving cancer cells of the amount of glucose they require.
Conventional medicine too often discounts the value of supplements, but many scientific studies demonstrate that supplements can substantially reduce cancer incidence.1
The key to more curative treatment is early detection. Good breast and prostate examination practices explain why the diagnosis rate for these cancers greatly exceeds the rate of fatality. Colon cancer would be more effectively treated if more people had regular colon examinations. Liver cancer is often due to chronic inflammation resulting from hepatitis. The hepatitis B virus can be prevented by vaccination.68 Hepatitis C virus is usually transmitted by unsafe intravenous drug or transfusion practices and unprotected sex, but is now controlled in over 90% of cases.69,70 Pancreatic cancer has been difficult to detect in early stages, which is why it is so often fatal. Cancer cells often release DNA into the bloodstream, which means that detecting cancer through blood tests (“liquid biopsies”) may be done in the future if standardized techniques can be developed.71
Notes on Cancer Prevention
There appears to be a link between salt intake and the bacterium Helicobacter pylori, which is associated with stomach cancer. It is possible that these two factors contribute to the development of the disease. In addition, salt intake and other dietary components are likely to damage the stomach mucosal lining, increasing the risk of stomach cancer.72 Risk of stomach cancer, colon cancer, and rectal cancer is probably increased by damage to mucous membranes from iron or N-nitroso compounds (NOCs) in red or processed meat.73-75Further damage is caused when cooking at high temperatures as this contributes to the formation of cancer-causing heterocyclic amines.76 Mucosal damage is also a reason why consuming more than two drinks of alcohol daily increases colorectal cancer risk.77 Any amount of alcohol consumption increases the risk of breast cancer in women because alcohol can convert estrogen into carcinogenic forms.78-81 For women with a BRCA1 mutation, surgical removal of the breasts can result in a reduced breast cancer risk.82,83
Animals that eat plants and fish that eat fish have increased concentrations of toxic metals in their flesh84,85and increased concentrations of organic toxins in their fat.86-88 Organic toxins like PCBs (polychlorinated biphenyls) persist in the environment and thus accumulate in fat tissue, increasing by many times the risk of melanoma skin cancer (for example).89 Because these toxins can damage DNA and cause cancer, a plant-based diet is safer than an animal-based diet. Chlorophyllin supplements can reduce the cancer-causing potential of toxin exposure.90,91 (See the December 2015 issue of Life Extension Magazine for more details.)
Selenium supplementation has been shown to reduce cancer incidence.92 A double-blind, randomized study showed that zinc supplements improved survival of cancer patients receiving radiation therapy.93 Vitamin D supplementation has been shown to reduce breast cancer incidence.94 Curcumin has been shown to inhibit breast cancer metastasis in mice.95 Higher quercetin intake is associated with reduced lung cancer incidence.96 A randomized, placebo-controlled trial of omega-3 fatty acid (EPA) supplementation showed significantly reduced polyp formation in subjects having an inherited predisposition to colon cancer.97 Life Extension Magazine has published many articles about nutrients which can reduce DNA damage by preventing inflammation and adverse gene expression changes, so the above is merely a sampling.
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