SCIENCE & NATURE

TheOptionsfor CancerPreventionBy Yousry Naguib, Ph.D.

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C ancer is a general term for more than 100 distinctdiseases characterized by uncontrolled, abnormalgrowth of cells in the body. Cancer cells canspread through the bloodstream and lymphatic sys-

tem to surrounding tissues (metastasis) within the body.Tumor metastasis is the most deadly characteristic of cancer.Unlike primary tumors that can be surgically removed andtreated with adjuvant chemotherapy and/or radiotherapy,metastases are difficult to treat and usually prove fatal.

Cancer affectsone in every three persons in developedcoun-tries. In 1999, more than 1.2 million new cases of cancer weredetected, and nearly half a million Americans died from someform of cancer. Breast cancer is the most common amongwomen, almost 175,000 new cases each year; while for men,prostate cancer is the second most prevalent form (180,000cases and 37,000 deaths in 1999)followinglung cancer.

Cancer is the second leading cause of death in the UnitedStates (heart diseaseis first).Currentestimatessay 30 percent ofallAmericanswill developsomekind of cancerin their lifetimes.

Evidence suggests that cancer could result from a number of

risk factors, including person's genetic make-up, immunesystem disorder, and exposure to radiation, sun's ultravio-let rays, tobacco, pollution, drugs such as DES (a syn-thetic estrogen), and a variety of chemicals such asasbestos, polycyclic, and aromatic hydrocarbons.

Cancer risk could be reduced by either preventingcarcinogenesis (DNA damage that leads to malignantcells), stopping carcinogenesis in its early stages orblocking the progression to invasive cancer. Dietary mod-ification and dietary supplements show considerablepromise as effective approaches for cancer prevention.

In the United States, 30 to 35 percent of cancercases are diet-related, and tobacco smoking causesanother 30 to 35 percent of total cancer cases. The dietrelated cancers include esophagus, stomach, liver,colon, pancreas, rectum, breast, prostate, and ovary.The dietary aspects most commonly associated withthese cancers are alcohol, nitrates, nitroso-amines, andfried foods. Popular diets, such as the Mediterraneanand Asian diets, have been shown to provide protectionagainst cancer due to a reduced intake of carcinogens(fewer processed foods) and an increased intake ofanti-carcinogenic phyto-nutrients.l

Mediterranean and Asian diets both tend to include

lots of fruits and vegetables, and small amounts of pro-tein (mostly fish) products. The Mediterranean diet alsoincludes a relatively high intake of olive and flax oils(which supply omega-3 fatty acids), while the Asian dietincludes a higher consumption of soy-based foods(which supply isoflavones).

DIETARY SUPPLEMENTS

Research studies appear to support the role of antioxidants,vitamins, minerals (selenium), and phyto-nutrients (flavonoids,carotenoids) in reducing the risk of certain cancers.2

Vitamin C, the primary water-soluble antioxidant nutrientin the diet, was found to be depleted in people afflicted withvarious cancers. Several studies have found a strong associa-tion between high dietary vitamin C intake (from foods) and areduced incidence of cancers of the stomach, bladder, throat,

colon and breast. Vitamin C has also been shown to regener-ate vitamin E, the major fat-soluble antioxidant in our body.

A case-control study in Sweden found that subjects with ahigh intake of vitamin C, beta-carotene, and alpha-tocophrolhad a 40 to 50 percent lower risk of esophageal cancer com-pared to subjects with a low intake of these nutrients. 3

Vitamin D-Analysis of data from the National Healthand Nutrition Examination Survey Epidemiological Studyrevealed that sunlight exposure and dietary vitamin D intakewere associated with reduced risk of breast cancer.4

Calcium-Data from a large case-control study, involving

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1,993 colon cancer cases and 2,410 controls, revealed thatdietary calcium was inversely associated with colon cancerrisk.s An ll-years followup study of 61,463 women found thatthose with the highest calcium intake (median 914 mg/day) hada reduced risk of colorectal cancer risk, suggesting that high cal-cium intake rnight lower colorectal cancer risk.6

Selenium deficiency has been associated with an increasedrisk of cancers of the prostate, colon, and lung.? In one study,subjects received either 200 mcg/day of selenium or a placebo.Those receiving the selenium supplements showed significantreductions in cancer of the prostate (66 percent), colon (50 per-cent), and lung (40 percent) as well as an overall 50 percentreduction in cancer deaths. Selenium in dietary supplementscomes from different sources, such as sodium selenite,selenomethionine, selenium-rich yeast, or high-selenium garlic.Higher doses of selenium, above 900 mcg-lmg per day, can leadto toxic effects, including gastrointestinal distress.

MGN-3 (Biobran) is a patented water-soluble polysaccha-ride called arabinoxylan, which is composed of a heIDi-celluloseextract of rice bran modified by enzymes from Shiitake mush-rooms. The main chemical structure of MGN-3 compound hasbeen identified as arabinoxylan with a xylose in its main chainand an arabinose polymer in its side chain.8a Research studiesshowed that MGN-3 works by stimulating the immune system,especially the natural killer (NK) cells. NK cells are the body'sfirst line of defense against cancer and viral infection.

Dr. Ghoneum at Drew University, Los Angeles, studiedMGN-3 on healthy control subjects and reported more than200 percent increase in NK activity after one to two weeks'treatment with MGN-3 at a daily dose of 30 to 45 mg perkilogram body weight.8b In a similar study involving cancerpatients, the increase in NK cell activity ranged from 145 per-cent to 332 percent in breast cancer patients, 174 percent to385 percent in prostate cancer patients, and 100 percent to240 percent in leukemia patients.8c

A characteristic feature unique to MGN-3 is that it does nothave a cycle off, cycle on phenomenon. This is known as hypo-responsiveness of NK activity and is associated with many bio-logical response modifiers (BRMs). Several studies showedthat single administration of BRMs significantly enhanced NKcell activity. However, repeated administration of the sameBRM result in depression of NK cell activity. It is interesting tonote that MGN-3 treatments were followed in 32 patients for 4years and NK activity was maintained at a high level with con-tinuation of treatments. This places MGN-3 at an advantageover other BRMs designed to boost NK activity.8c

In a most recent study Dr. Ghoneum discovered that can-cer cells exposed to MGN-3 become sensitive to chemothera-py, and could be killed by a low dosage of chemo. This dis-covery could help cancer patients requiring higher dosage ofchemo to reduce the dosage, thereby minimizing the harmfuleffects of high doses to healthy cells.

Beta-Carotene-Although evidence from epidemiologi-cal studies indicates that mixed carotenoids from fruits and

vegetables may provide protection against cancer, supplemen-tation with beta-carotene was actually found to promote cer-tain forms of cancer in specific populations (lung cancer inheavy smokers). Two large intervention studies known asAlpha- Tocopherol, Beta-Carotene (ATBC) study and Beta-

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Carotene and Retinol Efficacy Trial (CARET), showed a clear18-46 percent increase in lung cancer among smokers andthose exposed to asbestos. The ATBC study used 20 mg dosesof beta-carotene daily for 5-8 years. A related populationstudy, the Physicians' Health Study, found no adverse effectsof 25 mg/day of beta-carotene (but also no beneficial effect)but only about 10 percent of participants were smokers.9

Lycopene is another carotenoid (found in tomatoes, pinkgrapefruit, and watermelon) that has powerful antioxidant activ-ity and might be effective in prevention of prostate cancer.Giovannucci (1999), at Harvard Medical School, reviewing epi-demiologicalliterature, found that among 72 studies, 57 report-ed inverse associations between tomato intake or blood lycopenelevels and cancer risk. The evidence was particularly strong forcancers of the prostate, lungs, breast and stomach.lO

Grape Seed and Green Tea Extracts are both rich sourcesof polyphenols, which are potent antioxidants and possess anti-tumor properties (in animal studies). Grapes also contain resver-atrol and quercetin that also have potent antioxidant properties.The inhibitory action of tea (Camellia sinensis) and tea polyphe-nols against cancer formation has been demonstrated in differentanimal studies, which showed the ability of tea polyphenols toinhibit cell proliferation and induce apoptosis.ll In one test tubestudy, researchers have shown that green tea and its mainpolyphenol compound epigallocatechin-3 gallate (EGCC) todecrease the risk of breast cancer.12 Recommended dosage ofgreen tea supplements is in the range of 300-600 mg/day, equiv-alent to 3-6 cups of brewed green or black tea.

Isoflavones from soy or red clover possess both antioxi-dant and weak estrogenic activity. The anti-estrogen effect ofsmall doses of isoflavones, such as daidzein and genistein,might be beneficial in certain forms of hormone-sensitive can-cer, such as breast, uterine, and prostate.

A recent study showed that individuals with the highestlevels of daidzein, glycitein, and total isoflavones in theirurine samples had about half the cancer risk than those withthe lowest isoflavones levels. The study concluded that highintake of soy foods may reduce the risk of breast cancer. 13

In another recent study, pre-menopausal women betweenages 25 and 55, free of breast cancer, were randomly assignedto receive either a dietary supplement of isoflavones (40 mgper day) or a placebo for 12 weeks. The hormone estradioland its metabolite estrone (anticipated to be a carcinogen)decreased significantly in the isoflavone-group as comparedto the placebo. The study suggested that increased isoflavoneintake affects favorably estrogen metabolism, thereby demon-strating a potential to reduce the risk for breast cancer. 14

Garlic-The medicinal uses of garlic (Allium sativum)have a long history. Drawing and carvings of garlic wereuncovered in Egyptian tombs, dating from 3700 Be. Its usesas a remedy for heart disease, tumors and headaches are docu-mented in the Egyptian Codex Ebers, dating from 1550 BC.Recent studies have validated these health benefits. IS

Garlic may help reduce the risk of colon cancer by as muchas 30 percent-possibly via either its antioxidant properties(garlic is high in selenium) or its ability to influence certaindetoxification enzyme pathways in the liver. Several populationstudies in China, Europe, and the u.S. have shown that peoplewith the highest dietary consumption of garlic have a signifi-