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New study sheds light on why cancer often strikes those with healthy lifestyles August 21, 2018

Posted by Adam McLeod, former Naturopathic Doctor, BSc (Hons) in Cancer, cancer prevention, cancer therapy, Cancer Treatment, oncology, Research.
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Most cancer mutations are due to random DNA copying ‘mistakes,’ not inherited or environmental factors, Johns Hopkins researchers say.

A new study by scientists at Johns Hopkins provides evidence that random, unpredictable DNA copying “mistakes” account for nearly two-thirds of the mutations that cause cancer.

The researchers say their conclusions are supported by epidemiologic studies showing that approximately 40 percent of cancers can be prevented by avoiding unhealthy environments and lifestyles. But among the factors driving the new study, they add, is that cancer often strikes people who follow all the rules of healthy living—nonsmoker, healthy diet, healthy weight, little or no exposure to known carcinogens—and have no family history of the disease, prompting the pained question, “Why me?”

“It is well-known that we must avoid environmental factors such as smoking to decrease our risk of getting cancer. But it is not as well-known that each time a normal cell divides and copies its DNA to produce two new cells, it makes multiple mistakes,” says Cristian Tomasetti, assistant professor of biostatistics at the Johns Hopkins Kimmel Cancer Center and the Johns Hopkins Bloomberg School of Public Health. “These copying mistakes are a potent source of cancer mutations that historically have been scientifically undervalued, and this new work provides the first estimate of the fraction of mutations caused by these mistakes.”

Adds Bert Vogelstein, co-director of the Ludwig Center at the Kimmel Cancer Center: “We need to continue to encourage people to avoid environmental agents and lifestyles that increase their risk of developing cancer mutations. However, many people will still develop cancers due to these random DNA copying errors, and better methods to detect all cancers earlier, while they are still curable, are urgently needed,”

Tomasetti and Vogelstein’s research will be published Friday in the journal Science.

Current and future efforts to reduce known environmental risk factors, they say, will have major impacts on cancer incidence in the U.S and abroad. But they say the new study confirms that too little scientific attention is given to early detection strategies that would address the large number of cancers caused by random DNA copying errors.

“These cancers will occur no matter how perfect the environment,” Vogelstein says.

In a previous study authored by Tomasetti and Vogelstein in the Jan. 2, 2015, issue of Science, the pair reported that DNA copying errors could explain why certain cancers in the U.S., such as those of the colon, occur more commonly than other cancers, such as brain cancer.

In the new study, the researchers addressed a different question: What fraction of mutations in cancer are due to these DNA copying errors?

To answer this question, the scientists took a close look at the mutations that drive abnormal cell growth among 32 cancer types. They developed a new mathematical model using DNA sequencing data from The Cancer Genome Atlas and epidemiologic data from the Cancer Research UK database.

According to the researchers, it generally takes two or more critical gene mutations for cancer to occur. In a person, these mutations can be due to random DNA copying errors, the environment, or inherited genes. Knowing this, Tomasetti and Vogelstein used their mathematical model to show, for example, that when critical mutations in pancreatic cancers are added together, 77 percent of them are due to random DNA copying errors, 18 percent to environmental factors (such as smoking), and the remaining 5 percent to heredity.

In other cancer types, such as those of the prostate, brain, or bone, more than 95 percent of the mutations are due to random copying errors.

Lung cancer, they note, presents a different picture: 65 percent of all the mutations are due to environmental factors, mostly smoking, and 35 percent are due to DNA copying errors. Inherited factors are not known to play a role in lung cancers.

Looking across all 32 cancer types studied, the researchers estimate that 66 percent of cancer mutations result from copying errors, 29 percent can be attributed to lifestyle or environmental factors, and the remaining 5 percent are inherited.

The scientists say their approach is akin to attempts to sort out why “typos” occur when typing a 20-volume book: being tired while typing, which represents environmental exposures; a stuck or missing key in the keyboard, which represent inherited factors; and other typographical errors that randomly occur, which represent DNA copying errors.

“You can reduce your chance of typographical errors by making sure you’re not drowsy while typing and that your keyboard isn’t missing some keys,” Vogelstein says. “But typos will still occur, because no one can type perfectly. Similarly, mutations will occur, no matter what your environment is, but you can take steps to minimize those mutations by limiting your exposure to hazardous substances and unhealthy lifestyles.”

Tomasetti and Vogelstein’s 2015 study created vigorous debate from scientists who argued that their previously published analysis did not include breast or prostate cancers, and it reflected only cancer incidence in the United States.

Tomasetti and Vogelstein now report a similar pattern worldwide, however, supporting their conclusions. They reasoned that the more cells divide, the higher the potential for so-called copying mistakes in the DNA of cells in an organ. They compared total numbers of stem cell divisions with cancer incidence data collected by the International Agency for Research on Canceron 423 registries of cancer patients from 68 countries other than the United States, representing 4.8 billion people, or more than half of the world’s population. This time, the researchers were also able to include data from breast and prostate cancers. They found a strong correlation between cancer incidence and normal cell divisions among 17 cancer types, regardless of the countries’ environment or stage of economic development.

Tomasetti says these random DNA copying errors will only get more important as societies face aging populations, prolonging the opportunity for our cells to make more and more DNA copying errors. And because these errors contribute to a large fraction of cancer, Vogelstein says that people with cancer who have avoided known risk factors should be comforted by their findings.

“It’s not your fault,” says Vogelstein. “Nothing you did or didn’t do was responsible for your illness.”

In addition to Tomasetti and Vogelstein, Lu Li, a doctoral student in Tomasetti’s laboratory in the Department of Biostatistics at the Johns Hopkins Bloomberg School of Public Health, also contributed to the research.

Article retrieved from: https://hub.jhu.edu/2017/03/23/cancer-mutations-caused-by-random-dna-mistakes/

How is Sleep Linked to Cancer? August 27, 2015

Posted by Adam McLeod, former Naturopathic Doctor, BSc (Hons) in Cancer, Chemotherapy, Sleep.
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Written By: Dr. Adam McLeod, ND, BSc

Everyone knows the importance of a good nights sleep. It is no secret that your physical and mental health is negatively impacted when you do not get adequate sleep. Is lack of sleep actually linked to the formation of cancer? The short answer is yes and the reasons are obvious when you take a closer look at the science of sleep.

The circadian rhythm is a natural cycle in our brains that tells our cells whether it is day or night. This is a biological process that is present in virtually all forms of life and it helps to synchronize our biochemistry with the position of the sun. This internal clock obviously would be of great importance to our ancestors, however with our modern lifestyle we have become disconnected from the sun. There is a growing body of evidence that shows a link between disruptions in the circadian rhythm and the formation of cancer. In fact, some studies suggest that a circadian rhythm in chaos is a signal for a high risk of breast cancer even in the absence of mammographic evidence of neoplasm1.

People who work irregular shifts will naturally have disrupted circadian rhythms3,4. The reason is obvious; in what natural environment would anyone work at such irregular times and disregard their own internal clock. The effect is so dramatic that some researchers have called for shift work to be labeled a carcinogen2. It is also interesting to note that individuals who have mutations in genes related to this cycle have an increased risk of developing cancer6. The bottom line is that if your natural circadian rhythm is disrupted then you are more likely to develop cancer3,5.

What can be done to restore the health of your circadian rhythm? There are several key molecules that directly influence this delicate rhythm. Perhaps the best documented molecule is melatonin8,9. Melatonin is responsible for the generation of at least 40% of the amplitude of the circadian core body temperature rhythm7. Manipulation of melatonin levels are clinically useful to resynchronize the circadian rhythm under conditions of rhythm desynchronization. In other words, melatonin helps to restore the circadian rhythm when it has become disrupted.

Everyone has heard about melatonin and how it can be used to promote restful sleep. Melatonin is a critical component of the circadian rhythm, and it is one of the molecular signals that tells our cells whether it is day or night. I have seen countless times where cancer patients were prescribed melatonin by another Naturopathic doctor, but the patient discontinued it because they thought their sleep was fine. This suggests a misunderstanding between the patient and some of my colleagues regarding the reason for prescribing melatonin in the context of cancer. Whether the patient is sleeping well or not is secondary. They should be taking this supplement because of melatonin’s potent anti-cancer properties.

Melatonin triggers cell death in cancerous cells and it has several properties that make it useful as an adjunctive cancer therapy10,11,12. The conclusion from a paper in the prestigious journal “Cancer Research” stated that:

“Physiologic and pharmacologic concentrations of the pineal hormone melatonin have shown chemopreventive, oncostatic, and tumour inhibitory effects in a variety of in vitro and in vivo experimental models of neoplasia. Multiple mechanisms have been suggested for the biological effects of melatonin. Not only does melatonin seem to control development alone but also has the potential to increase the efficacy and decrease the side effects of chemotherapy when used in adjuvant settings.”

The use of melatonin is particularly indicated in cases of estrogen positive breast cancer. For those who are taking tamoxifen or letrozole as a long-term therapy, it is helpful to add melatonin into the treatment plan. The cancer prevention properties of melatonin appear to be mediated through the estrogen response pathway18.

When used appropriately, melatonin not only decreases side effects from chemotherapy, it also significantly enhances its effectiveness. In one randomized study, lung cancer patients were treated with chemotherapy alone or chemotherapy with melatonin. The melatonin group lived significantly longer with a reduced side effect profile14. This is just one example of many clinical trials. Melatonin can be used during chemotherapy or radiation, and the antioxidant effect is considered supportive of these conventional therapies15.

In my experience, the high doses of melatonin (20mg) are well tolerated when they are used properly. The most common complaint that I hear from patients is that they feel groggy the next morning. Upon further questioning, it becomes clear that they did not use the melatonin correctly. You must take it before bed; but after you take the melatonin, you must avoid light! This means no television, no iPads and no reading.

When light touches your eyes, it inhibits the activity of melatonin. This makes sense considering how connected melatonin is to the circadian rhythm. Think about it for a second. A thousand years ago when our ancestors went to sleep, they would not have encountered light again until the sun rose. When you are exposed to light after taking melatonin, it sends mixed messages to your brain and disrupts the circadian cycle. This often results in a sensation of grogginess the next morning. It is critical that after you take melatonin, you immediately go into a dark room and sleep.

One other interesting note about melatonin is how its metabolic effects are easily disrupted by magnetic fields13. The clinical significance of this disruption is unclear, but this is not surprising given how delicate the circadian rhythm is. What is also interesting is that magnetic fields appear to disrupt the positive benefit from tamoxifen as well16. This does not mean that everyone should panic and avoid all sources of magnetic fields since this is virtually impossible to do in modern day society. The threshold for this inhibitory effect is not well established, however, it is worthwhile to point out this interaction. Perhaps people wanting to prevent cancer should reduce their exposure to excessive magnetic fields when possible17.

Melatonin certainly can be helpful in an integrative cancer setting but you must have professional guidance when developing a cancer treatment plan. A Naturopathic Doctor can help you to develop a safe and effective treatment plan. Adam McLeod is a former Naturopathic Doctor (ND), BSc. (Hon) Molecular biology, Motivational Speaker and International Best Selling Author. He previously practiced at his clinic in Vancouver, British Columbia where he focused on integrative cancer care http://www.yaletownnaturopathic.com

1) Keith, Louis G., Jaroslaw J. Oleszczuk, and Martin Laguens. “Circadian rhythm chaos: a new breast cancer marker.” International journal of fertility and women’s medicine 46.5 (2000): 238-247.

2) Stevens, Richard G. “Light-at-night, circadian disruption and breast cancer: assessment of existing evidence.” International journal of epidemiology 38.4 (2009): 963-970.

3) Megdal, Sarah P., et al. “Night work and breast cancer risk: a systematic review and meta-analysis.” European Journal of Cancer 41.13 (2005): 2023-2032.

4) Hansen, Johnni. “Risk of breast cancer after night-and shift work: current evidence and ongoing studies in Denmark.” Cancer Causes & Control 17.4 (2006): 531-537.

5) Hansen, Johnni. “Increased breast cancer risk among women who work predominantly at night.” Epidemiology 12.1 (2001): 74-77.

6) Zhu, Yong, et al. “Non-synonymous polymorphisms in the circadian gene NPAS2 and breast cancer risk.” Breast cancer research and treatment 107.3 (2008): 421-425.

7) Cagnacci, A., J. A. Elliott, and S. S. Yen. “Melatonin: a major regulator of the circadian rhythm of core temperature in humans.” The Journal of Clinical Endocrinology & Metabolism 75.2 (1992): 447-452.

8) Kiss, K., et al. “Disturbed circadian rhythm in ICU patients as indicated by melatonin levels: a prospective pilot study.” Critical Care 19.Suppl 1 (2015): P549.

9) Flynn-Evans, Erin E., et al. “Circadian rhythm disorders and melatonin production in 127 blind women with and without light perception.” Journal of biological rhythms 29.3 (2014): 215-224.

10) Hill, Steven M., and David E. Blask. “Effects of the pineal hormone melatonin on the proliferation and morphological characteristics of human breast cancer cells (MCF-7) in culture.” Cancer research 48.21 (1988): 6121-6126.

11) Blask, David E., Leonard A. Sauer, and Robert T. Dauchy. “Melatonin as a chronobiotic/anticancer agent: cellular, biochemical, and molecular mechanisms of action and their implications for circadian-based cancer therapy.” Current topics in medicinal chemistry 2.2 (2002): 113-132.

12) Jung, Brittney, and Nihal Ahmad. “Melatonin in cancer management: progress and promise.” Cancer Research 66.20 (2006): 9789-9793.

13) Liburdy, R. P., et al. “ELF magnetic fields, breast cancer, and melatonin: 60 Hz fields block melatonin’s oncostatic action on ER+ breast cancer cell proliferation.” Journal of pineal research 14.2 (1993): 89-97.

14) Lissoni, P., et al. “Five years survival in metastatic non‐small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trial.” Journal of pineal research 35.1 (2003): 12-15.

15) Sanchez-Barcelo, Emilio J., et al. “Melatonin uses in oncology: breast cancer prevention and reduction of the side effects of chemotherapy and radiation.” Expert opinion on investigational drugs 21.6 (2012): 819-831.

16) Harland, Joan D., and Robert P. Liburdy. “Environmental magnetic fields inhibit the antiproliferative action of tamoxifen and melatonin in a human breast cancer cell line.” Bioelectromagnetics 18.8 (1997): 555-562.

17) Stevens, Richard G. “Electric power use and breast cancer: a hyptothesis.” Am. J. Epidemiol.;(United States) 125.4 (1987).

18) Sarkar, Fazlul H., and Yiwei Li. “Using chemopreventive agents to enhance the efficacy of cancer therapy.” Cancer Research 66.7 (2006): 3347-3350.

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