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Phytochemicals,
Nutrition and Chemoprevention

:  Harvey's Chocolates

The Round-Headed Kid Has a Sweet Experience  

Porting EGCG to the System

We present one possible way of improving the bioavailability of EGCG through oral and mucosal absorption of the potent phytochemical. Read Harvey's Chocolates to discover the formula, the sweetest way yet to get the phytochemical into your system.

 

:  The Virtues of Green Tea

Polyphenols, EGCG and Green Tea Extracts  

This article discusses the anti-cancer activity of green tea polyphenols.  Do You Like Drinking Green Tea?

 

The following are generally shorter articles, all presented together on this page.

:  Cancer Prevention Strategies

:  CLL Spouses

:  Hypercalcemia

:   Beta Glucan, Complement and Rituxan

:  Curcumin Interacts with Some Chemotherapy Drugs

:  Curcumin - II

:  Curcumin

:  Soy and Genistein

:  Green Tea Extract

: Cancer and Sugar Metabolism


Cancer and Sugar Metabolism                

4/14/2002

by Chaya Venkat

Did you know that roughly 40% of all cancer patients die of malnutrition, literally starved to death by their cancers?

We are all sensitized to watch out for the so-called "b-symptoms" of fatigue and weight loss, symptoms that tells the doctors that CLL is on the warpath. Did you ever wonder why even with extra helpings of Ben & Jerry's Chunky Monkey ice cream, the weight just kept dropping?

The key to the questions is sugar metabolism, and how healthy cells and cancer cells use this food as a source of energy. Back in 1931, Dr. Otto Heinrich Warburg first discovered that cancer cells have a fundamentally different energy metabolism compared to healthy cells. He was awarded the Nobel prize for this discovery.

Normal cells in the body use sugar as a fuel for cellular functions in an elegant and extremely efficient process called the Krebs cycle. In this process, sugar is "burned" using oxygen that we absorb through our lungs, and the final products are carbon dioxide and water. All of the energy in the sugar is completely wrung out in this aerobic process. There are times when the body's cells need energy in large quantities, and not enough oxygen is available to generate it by this aerobic process. An example is during vigorous exercise. When oxygen is limited, because your cells' energy needs outstrip your lungs capacity to supply oxygen, cells can derive energy from "anaerobic" (non-oxygen based) glycolysis. This is basically a type of fermentation of sugar, a process that does not need oxygen. This is a very inefficient way of producing energy, less than 5% of the total energy available from the sugar is actually generated in this way. A large amount of lactic acid is produced in the process, which is transported over time to the liver for further processing. You athletes out there, you can attest to the effect of build up of lactic acid in your muscles, the sense of tiredness and fatigue that accompanies.

Cancer cells have very high energy requirements, especially when they are growing rapidly in numbers. But they cannot utilize sugar, their favorite food source, with the efficiency of normal cells. They have defective mitochondria, which locks them into the anaerobic fermentation route. Put the two facts together, the high energy requirement of cancer cells and their inefficient use of sugar, and you can understand what is happening when you eat that extra slice of pecan pie. The sugar is basically going to feed the cancer, and the normal cells in your body get very little benefit from the consumed calories. Your liver has to work extra hard to boot, converting all that lactic acid. Sounds like a good thing, in our diet crazy culture, but not so good if you have CLL and the weight keeps dropping, no matter how many calories you eat.

The build up of lactic acid in the body as the cancer cells gobble up sugar may explain some of the fatigue symptoms, even though you have been taking it easy all day. (Another contributor to tiredness can be low levels of hemoglobin and red blood cells as a result of the CLL, causing anemia and poor oxygen transport in the body).

Here is an interesting tidbit. You may have heard of PET scan (positron emission tomography). This is an extremely accurate way of pinpointing the location of cancer cells in your body, much more effective than CAT scans or ultrasound. Guess how they do it: they give you a low dose of radioactive material, along with sugar, prior to the scan. The cancer cells absorb the sugar to the tune of 40 times more than the normal cells, and in the process they also get 40 times more of the radioactive tracer. The scan then looks for the sources of radiation in the body, thereby pin-pointing the location of the cancer cells. Even small clusters of malignant cells and very small malignant lymph nodes can be identified this way.

In hospitals, when a patient is wasting away and needs nutrition in a hurry, an intravenous drip of mostly glucose solution is used. In the case of cancer  patients, this would be like throwing gasoline on a fire, in an attempt to put it out. Slowly but surely, many hospitals are switching to low sugar, low carb  intravenous drips for cancer patients.

Yes, that's right, carbohydrates are also implicated. When there is not much sugar available, the body starts making some from other available nutrients. Carbohydrates are good candidates. Those of you who have had some experience with diabetes know that not all carbohydrates are created equal. There is something called glycemic index (GI), which measures how fast and easily a given carb gets converted to sugar. Heavily refined carbohydrates have a high GI, which is bad. Whole grain bread, for example is better than white Wonder bread. Vegetables are better than sugar rich fruits.

Want to starve your cancer cells, slow them down and make it really difficult for them to grow and flourish? You may want to consider drastically reducing your sugar intake; make like you are a diabetic, in terms of your dietary choices, even if you are not diabetic. Stay away from the candy and ice cream, it is not going to help you slow the weight loss, it will only feed your cancer. Concentrate on high protein diet, rich in low GI vegetables and carbohydrates. Actually, all of this is just simple good nutrition for any one, not just cancer patients.

I believe vigorous exercise plays a role too, in rapidly sopping up the easily available sugar in the blood stream. Basically your normal cells go into competition with the cancer cells for a limited resource, namely blood sugar. And normal cells have the advantage of being much more efficient in how they use the sugar. There have been several messages from members that document that their lymphocyte count did not grow during periods of vigorous exercise, such as getting into training to run a marathon.

This is an interesting and important subject, and useful in the sense that you can actually do something about your nutrition and exercise, as opposed to just waiting for that second shoe to drop. 

References:

http://www.cmbm.org/conferences/ccc99/transcripts99/f5.html

http://www.mercola.com/article/sugar/sugar_cancer.htm

http://www.mnwelldir.org/docs/nutrition/sugar.htm

Nutritional and physiological consequences of tumour glycolysis.

Dills W L Jr.

Department of Chemistry, University of Massachusetts at Dartmouth 02747.

A frequent characteristic of many malignant tumours is an increase in anaerobic glycolysis, that is the conversion of glucose to lactate, when compared to normal tissues. The causes of this intensification involve changes in enzyme and glucose transporter levels, shifts of the isoenzyme patterns in the cancer cells to those similar to foetal tissues and a breakdown in the normal control mechanisms, most notably the Pasteur effect. The host must adapt, with a corresponding increase in gluconeogenesis. This change, along with other adaptations made by the host, eventually results in the syndrome known as cancer cachexia, which is characterized by anorexia and depletion and redistribution of the host energy stores. In some ways many malignant tumours behave much like parasites, drawing upon the host for nutrients such as glucose and returning waste products such as lactate to the host for recycling or disposal. This cycling of glucose and lactate between host and tumour has been the target for a number of proposed and tested treatments, with regard to the possible  inhibition of tumour growth and/or possible prevention of some or all of the cachectic effects. Some of these suggested treatments have reached the point of clinical testing and show promise for continued research.
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[Metabolico-nutritional changes in the cancer patient]

[Article in Italian]

Rossi Fanelli F, Cangiano C, Muscaritoli M, Cascino A.

The severe impairment of the nutritional state, which usually accompanies malignant diseases, heavily contributes to the high morbidity and mortality rates observed in cancer patients. Nevertheless, the utility of an artificial energy supply to these patients is still controversial because the nutrients given to replete the host may also stimulate tumor growth. Consequently, a correct nutritional approach for cancer patients should be based upon a well-defined understanding of tumor as well as host-metabolic needs. In this regard, the most typical metabolic abnormalities observed in cancer patients and experimental animals are examined.

Specific modifications of the plasma levels of different groups of amino acids--including glucogenic, aromatic, sulphur-containing and branched-chain amino acids--have been observed in cancer patients independently of the their degree of malnutrition, glucose tolerance and tumor diffusion. This may reflect a series of specific modifications induced by the neoplastic tissue on host's protein turnover. Little information is available regarding the protein metabolism in the neoplastic tissue. A number of attempts have been made to reduce tumor growth by withholding single amino acids considered essential to the tumor;  nevertheless, the results obtained are still controversial. The two major abnormalities of carbohydrate metabolism observed in cancer patients are an increased glucose turnover and an impaired glucose tissue disposal. The former seems to be due to an increased glucogenesis, whereas the latter may be attributed to an insulin resistance in contrast to the high anaerobic glucose utilization observed in the neoplastic tissue.
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Green Tea Extract        

5/17/2002

by Chaya Venkat

There is a lot of recent interest in phytochemicals, complex molecules present in very small concentrations in plants and other food stuffs, that  nevertheless have significant impact on human health. Some of the "buzz" is a little off-the-wall, but some of it is getting accepted by main-stream medical research. It is frustrating trying to sort through all the hoopla that surrounds this field. In the next few articles I will write what I know in this area, but please be aware that not all that glitters is gold, and conversely sometimes really valuable and effective drugs are left undiscovered because of the mind-set of the medical establishment. It is a double edged sword, and the consumer needs to be really careful in making choices.

The cancer fighting capacity of green tea extract is one of them. (You would have to drink a lot of green tea, with all the associated caffeine etc, to get the required dosage of the particular phytochemical of interest, so much of the work centers on an extract of the green tea that concentrates this molecule). Others of interest are Curcumin (an extract from the bright yellow spice turmeric). Here too, you would have to consume unreasonable quantities of turmeric, since curcumin is present only in the range of 2-3% in the spice. Other phytochemicals of interest in fighting cancer are Genistein (extract of soy beans) and Artemisinin, extract of the Chinese herb wormwood.

Given below is an article that appeared on "CLL Research", on the topic of green tea extract. We can dig up a lot more stuff than given in this article, if there is a lot of member interest in this area. My own training is pretty hard core science, but I try to keep an open mind, and certainly in this discussion group I would like to try and avoid imposing any unreasonable bias.

Tea Time for Cancer

by: Michael Guthrie, R. Ph.

It seems a lot more people are drinking tea these days, especially green tea. Recent research has found that green tea contains some very powerful antioxidants. It appears that the workhorses in green tea are a group of compounds known as polyphenols. Green tea is manufactured from fresh, unfermented tealeaves. This process leaves the catechins, potent antioxidants, intact. The most well researched catechin is epigallocatechin gallate.

The interest in green tea really took off when a number of studies were published demonstrating that populations that consumed green tea had significantly lower incidences of many kinds of cancer including breast, stomach, liver, pancreatic, lung, skin and esophogeal. Catechins in green tea appears to prevent cancer by at least six different mechanisms.

1. They help to neutralize dietary carcinogens such as nitrosamine and aflatoxin.

2. They interfere with the binding of cancer-causing agents to cellular DNA, thereby protecting cells against mutations that can eventually cause cancer.

3. They protect against free-radical DNA damage that causes some cancers.

4. They inhibit bacterial-induced DNA mutations that also can lead to certain cancers.

5. They work with enzymes and other antioxidants in the intestine, liver and lungs to prevent the activation of certain carcinogens before they damage DNA.

6. They protect against the effects of ionizing radiation and ultraviolet radiation.

One researcher found that mice given green tea were half as likely to contract cancer than controls when injected with human non-Hodgkins lymphoma cells. Remarkably the chemotherapeutic drug cyclophosphamide was not able to reduce the incidence at all! (Bertolini, 2000).

A couple of recent studies shed light on the possible mechanism by which green tea exerts its anti-cancer effects. First, it appears that green tea up-regulates a tumor suppressor gene called p21. This allows the cell to stop its uncontrolled growth (Liberto, 2000). Another study indicates that green tea down-regulates NF Kappa B, a complex that contributes to uncontrolled cell growth. This allowed cancer cells to commit programmed cell death (Ahmad, 2000). A recent study done at the Karolinska Institute in Stockholm found another anti-cancer activity of green tea. It suppresses angiogenesis, which is the process of laying down blood vessels by cancer cells (Cao, 1999). Cancer cells depend on angiogenesis to form tumors. Still, another study found further anti-cancer activity with green tea. The study, done in Japan, found that epigallocatechin gallate (one of the main constituents of green tea), inhibits the secretions of collagenases. This deprives the cancer cells of a mechanism required for invasion of adjacent tissues (Sazuka, 1997).

Special benefits in prostate cancer: Two of the catechins in green tea have been found to be effective inhibitors of an enzyme that converts testosterone to dihydrotestosterone. Pharmaceutical products that have this effect have been shown to be effective in preventing prostate cancer (Liao, 1995)

One exciting finding about green tea has to do with its effect on telomerases. Telomeres are the genetic way of saying "the end" to cell division. In other words, a cell can only divide so many times. Cancer cells produce telomerases which destroy the telomeres allowing the cancer to divide without end (Naasani, et al, 1998). Still another finding with green tea is its suppression of a growth factor enzyme known as quinol oxidase (NOX). While expressed in normal cells while dividing, it is always expressed in cancer cells where it is called t-NOX. The researchers found that when exposed to the active ingredients in green tea, the cancer cells were unable to grow after division, and went into apoptosis (programmed cell death) (Moore, 1998).

References:

Ahmad N, Gupta S, Mukhtar H (2000). "Green tea polyphenol epigallocatechin-3-gallate differentially modulates nuclear factor kappaB in cancer cells versus normal cells." Arch Biochem Biophys Apr 15;376(2):338-46

Bertolini F et al (2000). "Inhibition of angiogenesis and induction of endothelial and tumor cell apoptosis by green tea in animal models of human high-grade non-Hodgkin's lymphoma." Leukemia Aug;14(8):1477-82

Cao Y et al, (1999). "Angiogenesis inhibited by drinking tea." Nature April1;398(6726):381 Kuroda Y., Y. Hara. (1999). 'Antimutagenic and anticarcinogenic activity of tea polyphenols.' Mutat Res 436: 69-97.

Liao S, Hipakka RA.( 1995). "Selective inhibition of steroid 5-alpha-reductase isozymes by tea epicatechin-3-gallate and epigallocatechin-3-gallate." Biochem Biophys Res Commun;214:833-38

Liberto M, Cobrinik D (2000) "Growth factor-dependent induction of p21(CIP1) by the green tea polyphenol, epigallocatechin gallate." Cancer Lett 2000 Jun 30;154(2):151-61

Morre D, Morre DJ. Findings on epigallocatechin gallate and tNOX inhibition presented at the 38th annual meeting of the American Society for Cell Biology; summary available at http://www.uns.purdue.edu

Sazuka M., S. Murakami, et al. (1995). 'Inhibitory effects of green tea infusion on in vitro invasion and in vivo metastasis of mouse lung carcinoma cells.' Cancer Lett 98: 27-31.
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Soy and Genistein        

5/19/02

by Chaya Venkat

Continuing on my theme of phytochemicals and how they impact a variety of very crucial systems in our bodies, here is a link to an article that tells you everything you have ever wanted to know (and more) on the effects of genistein. This is a pdf file, and you will need an Acrobat Reader in order to access it. The link is to an article is titled "Genistein: Effects that Oppose Cancer and Vascular Disease" by Christopher Brocci, Department of Chemistry, State University of New York at Albany. Be prepared for a small wait: the document is all of 65 pages long. Mr. Brocci has provided a bullet point summary of his paper at the following link: http://www.geocities.com/chrisbrocci/.

I will try and provide an overview of the role of soy in chemoprevention, in addition to this reading material for those of you who like to dig into things. 

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Curcumin                 

5/19/02

by Chaya Venkat

The active ingredient "Curcumin" is present in the spice turmeric, the bright yellow stuff that is invariably used in making curries, prepared mustard and even some cosmetics. Unfortunately, it is only present to the tune of about 1-3% in turmeric, and you will have to eat vast amounts of turmeric to get the required amounts of curcumin. Capsules with the potent extract curcumin are readily available. 

Another issue is the bio-availability of curcumin. It is digested in the gut and not very much of it gets into the blood stream. For that reason, its anti-cancer effects have been seen mostly in malignancies of the stomach, gut and colon etc. 

Recently it has been shown that the bio-availability of curcumin increases remarkably, when it is ingested with even minute quantities of piperine, an extract of pepper. (Ummm.. that hot curry using pepper and turmeric sounds better already).

Curcumin is rapidly entering main-stream medicine. You get a whole bunch of hits if you go to PubMed and just type in curcumin in the search engine. What I like about it is its total non-toxicity. People in India and elsewhere have been consuming large quantities of this stuff for hundreds of generations, with no side effects. In fact, turmeric has been heavily used in most ancient medical/herbal remedies.

Another point that I got during my search was that curcumin and soy genistein have a synergistic effect, the combined punch doing a much better job of chemoprevention and chemoproliferation than either by itself.

Epidemiology studies have some turned up some intriguing results. Given the level of environmental degradation and pollution of air, water and foodstuffs in some of the Asian countries, and the high percentage of people who smoke, some cancers are remarkably rare in these countries. For example, B-CLL in Japan is quite rare. But the percentage of Japanese who get B-CLL, after they have moved to the West and adopted Western diet is roughly the same as for the rest of the American population. The lower incidence of many of the cancers (not counting lung cancer, smoking is very popular in Japan) is attributed to the high consumption of soy products (and curcumin) in Japan. 

Here is a reference that has a ton of material on Curcumin, for those of you who want to dig in.

http://nr.stic.gov.tw/ejournal/ProceedingB/v25n2/59-66.pdf

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Curcumin - II

12/11/02

by Chaya Venkat

There seems to be a great deal of interest in this phytochemical derived from the spice turmeric. Some basic facts: 

Curcumin is present only to the tune of a few percent in turmeric. You will have to eat a lot of turmeric to get significant amount of curcumin. Also the absorption of curcumin into the blood is much more efficient in the presence of piperine, a compound present in pepper. There are companies that sell the right combination of curcumin and piperine.

There seems to be no toxicity associated with this phytochemical, even at extremely large doses. This is also borne out by the fact that it has been used for thousands of years in ethnic cuisine. 

Curcumin is known to be an anti-inflammatory, anti microbial and anti bacterial. It is also known to be a good blocker of the NF-kB pathway we discussed in previous articles.

Below is a website that has a lot of information and references about this interesting phytochemical. I am providing it so that you can browse through some of the information and draw your own conclusions. This is not an endorsement on my part. 

http://www.curcuminoids.com/content.htm

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Curcumin Interacts with Some Chemotherapy Drugs

12/20/02

by Chaya Venkat

Curcumin has been cited several times in this and other web sites as a chemo-preventive food based compound. While there seems to be a reliable amount of information on its non-toxicity, anti-biotic and germicidal properties, as well as anti-inflammatory characteristics as a result of blocking the important NF-kB pathway, the abstract below points out that it does interfere with the proper working of several major chemotherapy drugs.  I strongly  urge you to consult with your physician regarding use of any of these supplements, especially if you are about to start therapy of any kind.  

Abstract:

Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer Year: 2002 

Abstract No: 1801 Category: Tumor and Cell Biology Author(s): Robert Z Orlowski, Natalie A Edmund, Dominic T Moore, Yueyue Shi, Goerge W Small, Sivagurunathan Somasundaram, Univ of North Carolina at Chapel Hill, Chapel Hill, NC. 

Curcumin, the major component of the spice turmeric, is used as a coloring and flavoring additive in many foods, and has attracted interest because of its anti-inflammatory and chemopreventive activities. However, this agent also inhibits the c-Jun-N-terminal kinase (JNK) pathway, and since many chemotherapeutic drugs activate JNK signaling in the course of inducing apoptosis we hypothesized that curcumin might antagonize their anti-tumo  efficacy. Studies in tissue culture revealed that curcumin inhibited camptothecin-, mechlorethamine-, and doxorubicin-induced apoptosis of MCF-7, MDA-MB- 231, and BT-474 human breast cancer cells by up to 70% or more. Such inhibition of programmed cell death was concentration- and time- dependent, but occurred with even relatively brief exposures of three hours, or at curcumin concentrations of 1 micromolar, which have been documented in patients on a Phase I chemoprevention trial. Under  these conditions curcumin also inhibited JNK activation and mitochondrial release of  cytochrome c in a concentration-dependent manner. Using a murine xenograft model of human breast cancer the impact of dietary supplementation with curcumin at levels that reflect the intake of this agent in some human populations was tested on cyclophosphamide-mediated tumor regression. While treatment with cyclophosphamide induced a 36% decrease in the tumor weight of animals fed a regular diet, the weight of tumors in animals fed a curcumin-supplemented diet increased by 65% (p<0.001). Such dietary supplementation was accompanied by an in vivo decrease in the activation of apoptosis and JNK signaling by cyclophosphamide. 

These findings support the hypothesis that dietary curcumin can inhibit chemotherapy-induced apoptosis through blockade of JNK function, and suggest further studies to determine if breast cancer patients undergoing chemotherapy should avoid dietary supplementation with curcumin and limit their  exposure to curcumin-containing foods.
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Hypercalcemia

3/18/03

by Chaya Venkat

My thanks to a member who identified the following two useful  and authoritative links to information on hypercalcemia.

The first, provided by Novartis Pharmaceuticals:

http://www.us.novartisoncology.com/info/page/hypercalcemia 

and another from the National Cancer Institute:

http://www.meb.uni-bonn.de/cancer.gov/CDR0000062810.html

Both of these are excellent sites for getting a quick handle on calcium levels in your blood and what can happen if they get too high. 

A couple of actionable items that jump out from both sources:

1. Drink plenty of water!!

2. Try and get some exercise every day, just a walk around the block several times a day, if that is what you can manage. It would be great if you can also add some weight bearing exercises. 

3. Do not cut back on dietary calcium intake. The increase in calcium in your blood is caused by chemicals put out by the cancer cells that cause the calcium to be leached out of your bones. It also makes it harder for the body to absorb the necessary calcium from your diet, and the net result is weakened bones. The last thing you want is a nasty hip fracture or something like that, while you are trying to cope with CLL. This is also the basis of my strong negative reaction to high dose methylprednisone administration, especially if the patients are post menopausal women already at risk of osteoporosis. 

4. Getting your blood electrolytes measured is a simple and inexpensive test, something you should add to your routine monthly CBC monitoring. Perhaps not as frequently as your CBC, but I make sure my husband gets it done at least once a quarter. If your local oncologist does not see the need for it, print out some of the stuff in the above sites and revisit the topic. It really helps to be politely assertive in these matters. This is one simple way of keeping tabs on your blood calcium levels. 

5. As for coral calcium, please don't get me started on all that rubbish. I did catch a few minutes of an infomercial by "Dr". Barefoot the other day. What can I say, gullibility will kill you just as certainly as hypercalcemia. Not to mention it will deplete your bank account. I am sorry if this offends any of our members who are serious fans of Dr. Barefoot, but there it is. As a professional chemist, I can tell you for a fact that the absorption of "coral calcium" in your diet is no different than simple calcium tablets you can buy at the corner drugstore. 

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CLL Spouses

5/08/03

by Chaya Venkat

This article is for all of the CLL spouses and caregivers out there, who have seen first hand the effects of a cancer diagnosis in the family. I will now and for ever think of life as BC and AC, before cancer and after cancer diagnosis. It has changed our lives in ways that I still do not quite understand. For one, I never thought I would be pounding away on a computer close to mid-night, writing articles on a CLL patient support group. 

If in the process of taking care of your loved one you have neglected taking care of yourself, let things go a little in terms of nutrition, exercise and weight control, you ought to read the abstract below from the New England Journal of Medicine. Scary statistics. And the numbers are hugely credible, based on roughly a million U.S. adults. The message is clear: obesity kills, and it kills in many, many ways. Heart problems, diabetes, and cancers of all sorts feature strongly in their link to obesity. Our favorite CLL patients are not the only ones who need to be watching their nutrition, exercise and stress levels; it is only too easy to let things slide, let your own health become secondary and unimportant. And on this one I am not just doing the preaching, I am also one of the parties guilty as charged. And I am glad to report I am doing something about it. So should you. 

Abstract:

The New England Journal of Medicine, Volume 348:1625-1638 April 24, 2003 Number 17 

Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of U.S. Adults 

Eugenia E. Calle, Ph.D., Carmen Rodriguez, M.D., M.P.H., Kimberly Walker-Thurmond, B.A., and Michael J. Thun, M.D. 

Background: The influence of excess body weight on the risk of death from cancer has not been fully characterized. 

Methods: In a prospectively studied population of more than 900,000 U.S. adults (404,576 men and 495,477 women) who were free of cancer at enrollment in 1982, there were 57,145 deaths from cancer during 16 years of follow-up. We examined the relation in men and women between the body-mass index in 1982 and the risk of death from all cancers and from cancers at individual sites, while controlling for other risk factors in multivariate proportional-hazards models. We calculated the proportion of all deaths from cancer that was attributable to overweight and obesity in the U.S. population on the basis of risk estimates from the current study and national estimates of the prevalence of overweight and obesity in the U.S. adult population. 

Results: The heaviest members of this cohort (those with a body-mass index [the weight in kilograms divided by the square of the height in meters] of at least 40) had death rates from all cancers combined that were 52 percent higher (for men) and 62 percent higher (for women) than the rates in men and women of normal weight. For men, the relative risk of death was 1.52 (95 percent confidence interval, 1.13 to 2.05); for women, the relative risk was 1.62 (95 percent confidence interval, 1.40 to 1.87). In both men and women, body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin's lymphoma and multiple myeloma. Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in women. On the basis of associations observed in this study, we estimate that current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women. 

Conclusions: Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites. 

From the Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta. 

Address reprint requests to Dr. Calle at the American Cancer Society, 1599 Clifton Rd., NE, Atlanta, GA 30329.
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Cancer Prevention Strategies

10/5/03

by Judith E. Fisher, Ph. D.

Everyone knows that the word "chemotherapy" means using pharmaceuticals to treat cancer. But there's another important term that may be less familiar to you:  "chemoprevention,"  the use of pharmaceuticals to prevent cancer. 

Of course, the continued search for cancer treatments and cures is essential, but some scientists are taking a more proactive view. Instead of focusing on the "end-game" of treating cancer; they are looking for ways to identify pre-cancerous events and conditions so they can intervene before the cancer becomes a grave concern. 

It makes perfect sense, really. If pharmaceuticals can treat invasive cancers, then it seems reasonable to assume that pharmaceuticals and other substances might also be used to stop cancer in earlier stages. That idea is the basis for chemoprevention. 

Genetics and Environment:

Cancer occurs when a gene mutates unfavorably during the process of cell division. Since cell division is continuous, human cells undergo billions of divisions in a lifetime. Indeed, the longer we live, the greater the number of cell divisions…and the greater the chance that something will  eventually "go wrong" in the process. In some people, there is a genetic (family) predisposition for this kind of aberrant cellular event. In others, the mutation may be environmentally triggered. 

Although the possible combinations of heredity and environment seem virtually infinite, it is generally accepted that "...future cancer prevention strategies will hinge on studying both genetic profiles and environmental exposures."1  The overall goal of cancer prevention research is to determine WHO is likely to develop WHAT kind of cancer related to WHICH environmental trigger. Some day we may be able to take a pill that prevents the ravages of cancer in much the same way as we now have pills to lower blood pressure or reduce cholesterol.

Glimpses of the Future - Chemoprevention:

Many research studies point to factors that influence the development of cancer, and they offer us a glimpse into the potential for cancer chemoprevention. Various nutrients, phytochemicals (plant chemicals), and pharmaceuticals are already being investigated for use in chemoprevention. Here are some examples:

Nutrients may affect the development of cancer in some people.2

  • Deficiencies of vitamins B12 and B6 can damage replicating DNA and damage chromosomes, sometimes causing cancer.

  • A selenium deficiency may increase the incidence of epithelial cancers in some people.

  • Vitamin E may lead to reduced incidences of prostrate cancer.

  • Consuming some types of dietary fiber may help to prevent colorectal cancer in some people.

Some pharmaceuticals are already being investigated with regard to their potential in preventing cancer.3

  • Daily low-dose aspirin may lower the risk of colon cancer in some individuals.

  • Tamoxifen protects some high-risk women from breast cancer.

  • Raloxifene lowers cancer risk in some healthy women.

More than 4000 phytochemicals have been identified, and scientists are exploring how they may affect cancer risk and cancer development. "Some phytochemicals act as antioxidants but may also have a role in the formation of cancer-causing chemicals and/or the suppression of cancer development."4   Many studies are investigating various phytochemicals and their potential for cancer prevention - for example:

  • Polyphenols (catechins) in tea;

  • Carotenoid (beta carotene and lycopene) in carrots and tomatoes;

  • Indoles in cabbage and broccoli;

  • Isoflavones in soybeans and other legumes.

Potential Cancer Preventives

Source:  "Preventing Cancer" by Ricki Lewis in The Scientist,
Vol 17, Supplement 2|6| September 22, 2003.
 

Nutrients

Pharmaceuticals

Phytochemicals

Calcium

Anti-inflammatories

Carotenoids

Indole-3-carbinol

Fiber

NSAIDs

Curcumin

Isoflavones

Folate

Chromatin modifiers

Diallyl; sulfides

Isothiocyantes

Selenium

Nuclear receptor ligands

Green tea and grape polyphenols

L-perillyl alcohol

Vitamin D

 

Genistein

Saponins

Vitamin E

 

Indole-3-carbinol

Terpines

Ongoing Research Efforts:

A large number of studies have been aimed at advancing our knowledge of the causes of cancer and identifying substances that may prevent its occurrence or stamp it out in the early stages of development. The fact that the National Cancer Institute (NCI) has 60 ongoing clinical trials of chemopreventives5 signals the importance of chemoprevention as a proactive approach for fighting cancer.

References:

1 Ricki Lewis, "Preventing Cancer," in The Scientist, Vol 17, Supplement 2|6| September 22, 2003.   (You may register free at http://www.the-scientist.com/ and read the full article at: http://www.the-scientist.com/yr2003/sep/feature_030923.html).

2 & 3 Examples summarized from "Preventing Cancer" by Ricki Lewis.

4 "Phyto-Protect Your Health," UC Berkeley Wellness Letter, October, 2003.

5 "Preventing Cancer" by Ricki Lewis.  
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K  Phytochemicals, Nutrition and Chemoprevention               G  Contents                    : Current Articles