Health Conditions Detail



Cancer Prevention (Reducing the Risk)

Cancer is the second major cause of death (next to heart disease) in the United States. It claims the lives of more than half a million Americans each year out of the nearly 1.4 million who get the disease. The probability of getting cancer increases with age. Two-thirds of all cases are in people older than 65. 1
Cancer is believed to begin with a mutation in a single cell. However, a cell doesn't become cancerous overnight. Several mutations in a row are necessary to create all the characteristic features of cancer. Ordinarily, cells have a self-destruct mechanism that causes them to die when their DNA is damaged. However, in developing cancer cells, something interferes with the self-destruct sequence. It may be that the cancer-causing mutations themselves turn off the countdown.
The DNA alterations that create a cancer cell give it a certain independence from the ordinary rules of cell behavior. Normal cells are highly influenced by nearby cells, with the result that they "get along" well with their neighbors. For example, the growth of a healthy cell is ruled by special growth factors given off by surrounding tissues. However, cancer cells either grow without such growth factors or simply make their own. Many types of cancer cells can also trigger the growth of new blood vessels to feed them.
The rate of cancerous mutations is increased by exposure to carcinogenic substances. Cigarette smoke is a powerful carcinogen. Many carcinogens exist in the diet as well, even in fruits and vegetables.

Principal Proposed Natural Treatments

Before we can get into detailed discussion of natural products proposed to help prevent cancer, we must first discuss some fundamental issues regarding the nature of medical evidence.
It is rather difficult to prove that taking a certain supplement will reduce the chance of developing cancer. One really needs enormous long-term, double-blind, placebo-controlled studies in which some people are given the supplement while others are given placebo. However, relatively few studies of this type have been performed.
For most supplements, the evidence that they help prevent cancer comes from observational studies, which are much less reliable. Observational studies have found that people who happen to take in high levels of certain vitamins in their diets develop a lower incidence of specific cancers. However, in such studies it is very difficult to rule out other factors that may play a role. For example, individuals who take vitamins may also exercise more, or take better care of themselves in other ways. Such confounding factors make the results of observational studies less reliable.
Although this may sound like a theoretical issue, it has very practical consequences. For example, based primarily on observational studies, hormone replacement therapy was promoted as a heart-protective treatment for post-menopausal women. However, when placebo-controlled studies were performed, hormone replacement therapy proved to increase the risk of heart disease.
It is now thought that apparent benefits of hormone replacement therapy were due to the fact that woman who used it belonged to a higher socioeconomic class than those who did not use it. (For a variety of reasons, some of which are obscure, higher income is associated with improved health.)
Only a few supplements have any evidence from double-blind trials to support their potential usefulness for cancer prevention, and even that evidence is weak. For all other supplements, supporting evidence is limited to observational studies, as well as preliminary evidence from animal and test tube studies.
The results of observational trials have been mixed, but on balance, they suggest that high intake of vitamin E is associated with reduced risk of many forms of cancer, including stomach, mouth, colon, throat, laryngeal, lung, liver, and prostate cancer. 11,12,14-22,24,46,101,310
However, as noted above, the results of observational studies are unreliable as guidelines to treatment. The results of double-blind, placebo-controlled studies are far more persuasive in drawing conclusions about cause and effect. Unfortunately, on balance, these studies failed to find vitamin E helpful for the prevention of cancer. 9,13,51-53,263-265,280,301
The one positive note came in a double-blind study of 29,133 smokers. Those who were given 50 mg of synthetic vitamin E (dl-alpha-tocopherol) daily for 5 to 8 years showed a 32% reduction in the incidence of prostate cancer and a 41% drop in prostate cancer deaths. 9 Surprisingly, results were seen soon after the beginning of supplementation. This was unexpected because prostate cancer grows very slowly. A cancer that shows up in the prostate today actually started to develop many years ago. The fact that vitamin E almost immediately lowered the incidence of prostate cancer suggests that it may somehow block one of the last steps in the development of detectable prostate cancer.
Nonetheless, the negative results regarding most other types of cancer have made scientists hesitant to place too much hope in these findings. Some researchers believe that better results will be seen with a form of vitamin E called gamma-tocopherol rather than the alpha-tocopherol used in the trials mentioned above. 290 Others suggest that vitamin E might be more helpful for cancer prevention in low-risk people. Further research is currently underway to help settle these questions.
For more information, including dosage and safety issues, see the full Vitamin E article.

Selenium

It has long been known that severe selenium deficiency increases the risk of cancer. 29 One double-blind study found some evidence that selenium supplements might help prevent cancer even in the absence of severe deficiency. 30 The study actually designed to detect selenium's effects on skin cancer. It followed 1,312 individuals, half of whom were given 200 mcg of selenium daily. People participating in the study were not deficient in selenium. The participants were treated for an average of 2.8 years and were followed for about 6 years. Although no significant effect on skin cancer was found, the researchers were startled when the results showed that people taking selenium had a 50% reduction in overall cancer deaths and significant decreases in cancer of the lung (40%), colon (50%), and prostate (66%). The findings were so remarkable that the researchers felt obliged to break the blind and allow all the participants to take selenium.
Subsequent re-evaluation of the results, including additional data from follow-up, indicated that lung cancer and colon cancer benefits were seen only in participants with somewhat low levels of selenium in the blood to begin with. 54,266 (At the time of this writing, researchers had not announced whether the same was true regarding prostate cancer prevention.)
While this evidence is promising, it has one major flaw: The laws of statistics tell us that when researchers start to deviate from the question their research was designed to answer, the results may not be trustworthy. As an illustration of this, yet another after-the-fact statistical analysis of the data hints selenium supplements might actually increase risk of certain forms of skin cancer. 250 This, however, may not be a real concern either, as all such statistical manipulation is suspect.
One study published in 2007 evaluated whether selenium supplements could help prevent skin cancer in transplant patients. 285 People who have undergone organ transplants are at particularly high risk of skin cancer linked to the human papilloma virus (HPV). In this double-blind study, 184 organ transplant recipients were given either placebo or selenium at a dose of 200 mg daily. The results over two years failed to show benefit: both the placebo and the selenium group developed precancerous and cancerous lesions at the same rate. The bottom line: Further research will be necessary before we know whether selenium supplements actually help prevent cancer.
For more information, including dosage and safety issues, see the full Selenium article.

Mixed Antioxidants

A large double-blind, placebo-controlled study evaluated the potential overall cancer preventive benefits of a low-dose combination antioxidant supplement providing 120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta-carotene, 100 mcg of selenium, and 20 mg of zinc taken daily for about 7.5 years. 251 The results as a whole failed to show benefit. However, analysis by sex showed a significant reduction in cancer incidence in men but not in women. It is not clear whether these results are meaningful. The researchers involved in this study concluded the following: Low dose antioxidant supplementation may be helpful in healthy people, without cancer risk, who are deficient in antioxidant nutrition. High doses of antioxidants may be harmful for people who are at higher risk for cancer and may already be in the initial phases of cancer development. Finally, antioxidants in high or low doses are probably not helpful in healthy people with good nutrition. 279
Another large study failed to find mixed antioxidants helpful for preventing stomach cancer in particular. 284 And, in a meta-analysis (detailed mathematical review) of 20 high-quality, randomized trials (involving a total of 211,818 participants), researchers concluded that neither beta-carotene, vitamin A, vitamin C, vitamin E, or selenium effectively lowered the risk of gastrointestinal cancers. If anything, they may have slightly increased the risk of death from these cancers. 308
On the other hand, a review of 22 case-controlled studies with 10,073 women did find evidence that vitamin or antioxidant supplementation may reduce the risk of cervical dysplasia (which can lead to cervical cancer). 319 Supplements that may offer this protective benefit include beta-carotene , vitamin C , vitamin E , and vitamin B12 . While these results seem more promising, case-controlled studies are less reliable than randomized, controlled studies and sometimes serve to cloud the picture rather clarify it.

Beta-carotene

The story of beta-carotene and cancer is full of contradictions. It starts in the early 1980s, when the cumulative results of many studies suggested that people who eat a lot of fruits and vegetables are significantly less likely to get cancer. 55,56 A close look at the data pointed to carotenes as the active ingredients in fruits and vegetables. It appeared that a high intake of dietary carotene might significantly reduce the risk of cancers of the lung, 57 bladder, 58 breast, 59 esophagus, 60 and stomach. 11
However, as noted above, observational studies cannot prove cause and effect. When researchers gave beta-carotene to study participants, the results have been impressively negative.
Most studies enrolled people in high-risk groups, such as smokers, because it is easier to see results when you look at people who are more likely to develop cancer to begin with.
The anticancer bubble burst for beta-carotene in 1994 with the results of the Alpha-Tocopherol, Beta-carotene (ATBC) study. 13 These results showed that beta-carotene supplements did not prevent lung cancer, but actually increased the risk of getting it by 18%. This trial followed 29,133 male smokers in Finland who took supplements of about 50 IU of vitamin E (alpha-tocopherol), 20 mg of beta-carotene (more than 10 times the amount necessary to provide the daily requirement of vitamin A), both, or placebo daily for 5 to 8 years. (In contrast, vitamin E was found to reduce the risk of cancer, especially prostate cancer.)
In January 1996, researchers monitoring the Beta-carotene and Retinol Efficacy Trial (CARET) confirmed the prior bad news with more of their own: The beta-carotene group had 46% more cases of lung cancer deaths. 64 This study involved smokers, former smokers, and workers exposed to asbestos. Alarmed, the National Cancer Institute ended the $42 million CARET trial 21 months before it was planned to end.
At about the same time, the 12-year Physicians' Health Study of 22,000 male physicians was finding that 50 mg of beta-carotene (about 25 times the amount necessary to provide the daily requirement of vitamin A) taken every other day had no effect—good or bad—on the risk of cancer or heart disease. In this study, 11% of the participants were smokers and 39% were ex-smokers. 65,66
Similarly, another study of beta-carotene supplements failed to find any effect on the risk of cancer in women. 67 And, in a final indictment of beta-carotene’s safety and effectiveness, researchers, who combined the results of 12 recent placebo-controlled trials investigating the association between antioxidant supplementation and cancer, found that beta-carotene use was associated with an increased incidence of cancer among smokers. 304 But the story doesn’t end there. In yet another careful analysis of 4 randomized trials involving 109,394 smoker and former-smokers, researchers found that current smokers who consumed between 20-30 mg of beta-carotene were at significantly greater risk of developing lung cancer. There was no such risk among former smokers. 305
What is the explanation for these discrepancies? One possibility is that beta-carotene alone is not effective. Fruits and vegetables contain many carotenoids (carotene-like substances) that may be more important for preventing cancer than beta-carotene. One researcher has suggested that taking beta-carotene supplements actually depletes the body of other beneficial carotenoids. 69
It is also possible that intake of carotenes as such are unrelated to cancer and that some unrelated factor common to individuals with a high carotene diet is the cause of the benefits seen in observational trials.
For more information, including dosage and safety issues, see the full Beta-carotene article.

Tomatoes (Lycopene)

Lycopene, a carotenoid like beta-carotene, is found in high levels in tomatoes and pink grapefruit. Lycopene appears to exhibit about twice the antioxidant activity of beta-carotene and may be more helpful for preventing cancer.
In one observational study, elderly Americans consuming a diet high in tomatoes showed a 50% reduced incidence of cancer. 70 Men and women who ate at least seven servings of tomatoes weekly developed less stomach and colorectal cancers compared to those who ate only two servings weekly.
In another study, 47,894 men were followed for 4 years in an observational study looking for influences on prostate cancer. 71 Their diets were evaluated on the basis of how often they ate fruits, vegetables, and foods containing fruits and vegetables. High levels of tomatoes, tomato sauce, and pizza in the diet were strongly connected to reduced incidence of prostate cancer. After an evaluation of known nutritional factors in these foods as compared to other foods, lycopene appeared to be the common denominator. Additional impetus has been given to this idea by the discovery of lycopene in reasonably high levels in the human prostate, 72 evidence from test tube studies that lycopene might slow DNA synthesis in prostate cells, 281 and evidence that men with higher lycopene levels in the blood have a lower risk of prostate cancer. 73
Similarly weak evidence suggests that foods containing lycopene might help prevent other forms of cancer as well, including lung, colon, and breast cancer. 68,74,112
A few poorly designed intervention trials have also been performed, and these suggest that lycopene or a standardized tomato extract containing lycopene might be helpful for the prevention or treatment of prostate or breast cancer. 267-269
For more information, including dosage and safety issues, see the full Lycopene article.

Vitamin C

Several observational studies have found a strong association between high dietary vitamin C intake and a reduced incidence of stomach cancer. 76,78 It has been proposed that vitamin C may prevent the formation of carcinogenic substances known as N-nitroso compounds in the stomach.
Observational studies have also linked higher vitamin C in the diet with reduced risk of cancers of the colon, esophagus, larynx, bladder, cervix, rectum, breast, and perhaps lung. 12,76,79,82-84 However, dietary vitamin C intake does not appear to be associated with reduced rate of prostate cancer. 85
One study found that vitamin C supplementation at 500 mg or more daily was associated with a lower incidence of bladder cancer. 86 However, another study found no association. 87 Similarly, in another observational study, 500 mg or more of vitamin C daily over a period of 6 years was not associated with reduced incidence of breast cancer. 89 Another study found similar results. 90
For more information, including dosage and safety issues, see the full Vitamin C article.

Green Tea

Both green tea and black tea come from the plant Camellia sinensis , which has been cultivated in China for centuries. The key difference between the two is in preparation. For black tea, the leaves are allowed to oxidize, a process believed to lessen the potency of the presumed active ingredients in green tea, catechin polyphenols. Green tea is made by lightly steaming the freshly cut leaf, a process that prevents oxidation and possibly preserves more of the therapeutic effects.
Laboratory and animal studies suggest that tea consumption protects against cancers of the stomach, lung, esophagus, duodenum, pancreas, liver, breast, and colon. 91,92 A 1994 study of skin cancer in mice found that both black and green teas, even decaffeinated versions, inhibited skin cancer in mice exposed to ultraviolet light and other carcinogens. 93,94 After 31 weeks, mice given the teas brewed at the same concentration humans drink had 72% to 93% fewer skin tumors than mice given only water.
However, results from observational studies in humans have not been so clear-cut—some have found evidence of a protective effect, and others have not. 95
One study followed 8,552 Japanese adults for 9 years. 96 Women who drank more than 10 cups of green tea daily had a delay in the onset of cancer and also a 43% lower total rate of cancer occurrence. Males had a 32% lower cancer incidence, but this finding was not statistically significant.
A study in Shanghai, China, found that those who drank green tea had significantly less risk of developing cancers of the rectum and pancreas than those who did not. No significant association with colon cancer incidence was found. 97 A total of 3,818 residents aged 30 to 74 were included in the population study. For men, those who drank the most tea had a 28% lower incidence of rectal cancer and a 37% lower incidence of pancreatic cancer compared to those who did not drink tea regularly. For women, the respective differences in cancer frequency were even greater: 43% and 47%.
Another study in Shanghai found similar associations for stomach cancer. Green tea drinkers were 29% less likely to get stomach cancer than nondrinkers, with those drinking the most tea having the least risk. 98 Interestingly, the risk of stomach cancer did not depend on the person's age at which he or she started drinking green tea. Researchers suggested that green tea may disrupt the cancer process at both the intermediate and the late stage.
Green tea may exert an estrogen-blocking effect that is helpful in preventing breast and uterine cancer, 103 and another study suggests that it might prevent the development of tumors by blocking the growth of new blood vessels. 104 A review of 9 studies (none of which were clinical trials) involving over 5,600 cases of breast found weak evidence for reduction in breast cancer recurrence among people who consumed more than 3 cups of green tea every day. 317 But, they failed to find reliable evidence for a reduction in the incidence of breast cancer.
However, in an observational study of 26,311 Japanese individuals, researchers saw no reduction in stomach cancer rates. 99 Lack of benefit was also seen in a study conducted in Hawaii. 100 And, combining the results of 13 observational studies, researchers found conflicting evidence for green tea’s effect on the risk of stomach cancer. 312 However, in a small Japanese randomized trial, patients who supplemented their regular diet with an extra 1.5 g of green tea extract per day for 1 year lowered their risk of recurrent colorectal polyps compared to those who took no supplement. 313
In a review of multiple studies including 43 observational studies, 4 randomized trials and 1 metanalysis (mathematical summation of the results from several studies), researchers concluded that there was inconsistent evidence supporting green tea’s effectiveness for cancer prevention. 311
The main catechin polyphenol found in green tea is epigallocatechin gallate (EGCG). Preliminary experimental studies suggest that EGCG may help prevent skin cancer if it is applied directly to the skin. 102
For more information, including dosage and safety issues, see the full Green Tea article.

Soy

In many animal studies, soybeans, soy protein, or other soy extracts decreased cancer risk, and observational studies in people have found suggestive associations between higher soy consumption and lower incidence of hormone-related cancers such as prostate, breast, and uterine cancer. 105-111
Soybeans provide estrogen-like compounds known as isoflavones , especially genistein and daidzein. These substances bind to the same sites in the body as estrogen, occupying these sites and keeping natural estrogen away. Estrogen stimulates certain forms of cancer, but soy isoflavones exert a milder estrogen-like effect that may not stimulate cancer as much as natural estrogen. This could help protect against cancer. Soy may additionally reduce levels of the body’s own estrogen, which would also have a protective effect. 2,3,15,22,44,82
However, not all evidence on soy and cancer is positive. Because the isoflavones work somewhat like estrogen, there are theoretical concerns that they may not be safe for women who have already had breast cancer. Studies in animals have found suggestive evidence that under certain circumstances soy isoflavones might stimulate breast cancer cells. 60,61,63 Furthermore, evidence from two preliminary studies in humans found changes suggesting that soy might slightly increase breast cancer risk. 3,65 Other studies in women have found reassuring results; nonetheless, prudence suggests that women who have had breast cancer, or are at high risk for it, should consult a physician before taking any isoflavone product. 75
Men have very low levels of circulating estrogen, so the net effect of increased soy consumption might be to increase estrogen-like activity in the body. Since real estrogen is used as a treatment to suppress prostate cancer, it has been hypothesized that the mild estrogen-like activity of isoflavones has a similar effect. There are also indications that isoflavones might decrease testosterone levels, and alter ratios of certain forms of estrogen, both of which would be expected to provide benefit. 297,298 Thus, there are several possible ways in which isoflavones might be useful for preventing or treating prostate cancer. Whether or not they actually help has been tested in a few preliminary trials.
For example, in one double-blind study, men with early prostate cancer were given either isoflavones or placebo, and their PSA levels were monitored. 252 (PSA is a marker for prostate cancer, with higher values generally showing an increased number of cancer cells.) The results did show that use of isoflavones (60 mg daily) slightly reduces PSA levels. Whether this meant that soy actually slowed the progression of the cancer or simply lowered PSA directly is not clear from this study alone. However, another study of apparently healthy men (not known to have prostate cancer) found that soy isoflavones at a dose of 83 mg per day did not alter PSA levels. 299 Taken together, these two studies provide some direct evidence that soy isoflavones may be helpful for treating or preventing prostate cancer, but the case, nonetheless, remains highly preliminary.
A special highly concentrated extract of soy, Bowman-Birk Inhibitor (BBI), has also shown promise for helping to prevent various types of cancer. 286-289
There exists weak evidence that besides the isoflavone found in soy, flavonoids (found, for example, in beans, onions, apples, and tea) may reduce the recurrence of colorectal polyps, common precancerous lesions found in the colon and rectum. 307
For more information, including dosage and safety issues, see the full Soy article.

Folate

Observational studies have suggested that folate deficiency may predispose individuals toward developing cancer of the cervix, 120 colon, 121,122 lung, 123 breast, 124 pancreas, 125 and mouth. 123 Other observational studies have suggested that folate supplements may help prevent colon cancer, especially when it is taken for many years, or by people with ulcerative colitis . 20,127,129,253,290 However, observational studies are notoriously unreliable; large double-blind, placebo-controlled studies are needed to prove a treatment effective. One such study performed on folate for cancer prevention among 1,000 people over a 5-year period found folate ineffective for preventing early colon cancer. 140 And, in a large controlled trial involving over 5,400 women, supplements combining folate plus vitamins B 6 and B 12 taken for 7 years did not reduce the risk of a cancer compared to a placebo. 315 However, a much smaller study involving 94 individuals with colon polyps (a precancerous condition) found that folate may reduce the risk of recurrent polyps over a 3-year period. 309
For more information, including dosage and safety issues, see the full Folate article.

Other Proposed Natural Treatments

Some, but not all, observational and intervention studies have found evidence that calcium supplementation may reduce the risk of colon cancer. 130-139,270-272,302 Risk reduction might continue for years after calcium supplements are stopped. 283 In men, however, calcium supplements might increase risk of prostate cancer. 273-274 For menopausal women, calcium supplementation, especially when taken along with vitamin D, appears to reduce overall cancer incidence. 292
Some studies have connected higher vitamin D levels with a lower incidence of cancer of the breast, colon, pancreas, and prostate, as well as melanoma, but overall research has yielded mixed results. 130,140-142,144-159,275,314 In an extremely large study involving over 36,000 post-menopausal women, supplementing the diet with 1,000 mg of calcium plus 400 IU of vitamin D daily did not lower the risk of breast cancer over a period of 7 years. 316 Based on the results of this placebo-controlled study, there does not appear to be a connection between vitamin D and breast cancer risk.
Increasing dietary fiber has long been thought to help reduce the incidence of colon polyps (a risk factor for colon cancer). 160-163 Several studies, though, have found either little evidence of benefit or none at all. 41,165-170 For example, one very large study enrolled almost 2,000 people with a history of colon polyps and compared the ordinary American diet against a diet very high in fiber, fruits and vegetables, as well as low in saturated fat. 294 Over the four years of the study, plus an additional four years of follow-up, this presumably “healthier” diet failed to reduce polyp recurrence. Conversely, a 2011 systematic review involving 25 observational studies did find evidence to support high-fiber diets. 318 Researchers found that people who ate a diet high in fiber (10 g daily of total dietary fiber) had a reduced risk of developing colorectal cancer. Cereal fiber and whole grains appeared to be more beneficial than other types of fiber (eg, fruits, vegetables, or legumes).
Substances known as lignans are found in several foods and may produce anticancer benefits. They are converted in the digestive tract to estrogen-like substances known as enterolactone and enterodiol. 106,172 Like soy isoflavones (see the previous discussion under the heading Soy ), these substances prevent estrogen from attaching to cells and may thereby block its cancer-promoting effects. Lignans are found most abundantly in flaxseed , a high-fiber grain that has been cultivated since ancient Egyptian times. Both flaxseed and flaxseed oil have been recommended for prevention or treatment of cancer, but the supporting evidence is still extremely preliminary. 106,173-176,178-181 Contrary to some reports, flaxseed oil contains no lignans. 173 Instead, it contains the alpha-linolenic acid, which is also hypothesized to have cancer-preventive effects.
Evidence from observational studies suggests that garlic taken in the diet as food may help prevent cancer, particularly cancer of the colon and stomach. 36-43 In one of the best of these studies, the Iowa Women's Study, women who ate significant amounts of garlic were found to be about 30% less likely to develop colon cancer. 41,44 Similar results were seen in other observational studies performed in China, Italy, and the United States. 37,45,295 In addition, one preliminary intervention trial also found a bit of evidence that aged garlic may reduce risk of colon cancer. 296
Resveratrol is a phytochemical found in at least 72 different plants, including mulberries and peanuts. Grapes and red wine are particularly rich in resveratrol. This substance has shown anticancer properties in test tube studies. 186,187
One large observational study suggests that higher intake of boron may reduce risk of prostate cancer. 204
Provocative evidence suggests that a substance called sulforaphane , found in broccoli and related vegetables, may possess anticancer properties. 205,207 Recently, broccoli sprouts have been touted for cancer prevention on the basis of their high content of sulforaphane. However, this recommendation is still highly speculative. Another constituent of broccoli-family vegetables, indole-3-carbinol , has also shown promise as a cancer-preventative agent; 208-212 however, there is some evidence that this substance might actually increase the risk of cancer in certain circumstances. 213,214 Much the same is true of the related substance diindolylmethane (DIM).
In one large randomized controlled trial, diets rich in fish and omega-3 fatty acids from fish were associated with a significant reduction in the risk of developing colorectal cancer among men over a 22-year period. 306 Another study provides preliminary supporting evidence for the notion that fish oil reduces the risk of prostate cancer. 222 However, on balance, there is still relatively little evidence that the consumption of fish oil reduces the risk of cancer. 276 For example, a secondary analysis of a large trial including 2,501 adults with a history of heart attack, angina, or stroke did not find an association between omega-3 fatty acids (with or without the addition of B vitamins) and risk of cancer. 320
Weak evidence hints that N-acetylcysteine (NAC) treatment may help to prevent colon cancer. 223
Several studies have experimented with using very high doses of vitamin A to prevent skin cancer, doses considerably above levels ordinarily considered safe. Some have found possible benefits regarding preventing some forms of skin cancer, while others have not. 256-258 This approach should not be tried except under physician supervision.
Vitamin K has shown a slight bit of promise for helping to prevent liver cancer in people with chronic viral hepatitis. 259
Innumerable other herbs and supplements have shown minimal promise in test tube and animal studies, including but not limited to active hexose correlated compound (AHCC), cordyceps , Coriolus versicolor , ligustrum , quercetin , citrus bioflavonoids , conjugated linoleic acid , Morina citrifolia ( noni ), turmeric , rosemary , betulin (from white birch tree), bromelain , ellagic acid (from grapes, raspberries, strawberries, apples, walnuts, and pecans), ginseng , glycine , grass pollen , inositol hexaphosphate (phytic acid, IP6), kelp , licorice , melatonin , MSM , milk thistle , nettle , OPCs (oligomeric proanthocyanidins) , papaw tree bark, probiotics or "friendly" bacteria, royal jelly , shiitake , schisandra , and blue-green algae . 80,105,184,187,216-218,219,220,221,224-249,255,293
While it is commonly stated as a fact that high consumption of fruits and vegetables reduces cancer risk, the evidence is limited to inherently unreliable observational studies, and even among these the results are inconsistent. 126,128,143,164,171,177,182,183,260 As noted earlier, a large study failed to find that a diet high in fruits and vegetables reduced risk of colon polyps. 294 An analysis, however, of 19 prospective (forward-looking) observational studies including over a million people did find a weak association between diets high in fruits and vegetables and a reduced risk of developing colorectal cancer. 321 Those who had the highest intake of fruits and vegetables had a significantly lower risk compared to those with the least intake.
Similarly, meat consumption, widely stated to increase colon cancer risk, might or might not do so—the evidence is not compelling. 81,261 Current data does not suggest that diets high in sugar or other simple carbohydrates increase colon cancer risk, 262 or that reducing fat in the diet reduces colon, uterine, or breast cancer risk. 277-278,300,303
Higher level of exercise might potentially help reduce the risk of various forms of cancer, especially colon cancer. 282

References

1 Longo D. Approach to the patient with cancer. In: Fauci AS, Wilson JD, Martin JB, et al, eds. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill; 1998.

2 Xu X, Duncan AM, Merz BE, et al. Effects of soy isoflavones on estrogen and phytoestrogen metabolism in premenopausal women. Cancer Epideimiol Biomarkers Prev. 1998;7:1101-1108.

3 Persky VW, et al. Effect of soy protein on endogenous hormones in postmenopausal women. Am J Clin Nutr. 2002;75:145-153.

4 Chatenoud L, La Vecchia C, Franceschi S, et al. Refined-cereal intake and risk of selected cancers in Italy. Am J Clin Nutr. 1999;70:1107-1110.

5 Osborne M, Boyle P, Lipkin M. Cancer prevention. Lancet. 1997;349(suppl 2):27-30.

6 Smith-Warner SA, Spiegelman D, Yaun SS, et al. Intake of fruits and vegetables and risk of breast cancer: a pooled analysis of cohort studies. JAMA. 2001;285:769-776.

7 Terry P, Wolk A, Persson I, et al. Brassica vegetables and breast cancer risk [letter]. JAMA. 2001;286:2975-2977.

8 Smith-Warner SA, Willett WC, Spiegelman D, et al. Brassica vegetables and breast cancer risk [letter]. JAMA. 2001;285:2977.

9 Heinonen OP, Albanes D, Virtamo J, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst. 1998;90:440-446.

10 Helzlsouer KJ, Huang HY, Alberg AJ, et al. Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer. J Natl Cancer Inst. 2000;92:2018-2023.

11 Zheng W, Sellers TA, Doyle TJ, et al. Retinol, antioxidant vitamins, and cancers of the upper digestive tract in a prospective cohort study of postmenopausal women. Am J Epidemiol. 1995;142:955-959.

12 Esteve J, Riboli E, Pequignot G, et al. Diet and cancers of the larynx and hypopharynx: the IARC multi-center study in southwestern Europe. Cancer Causes Control. 1996;7:240-252.

13 Albanes D, Heinonen OP, Huttunen JK, et al. Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. Am J Clin Nutr. 1995;62(suppl):1427S-1430S.

14 Chen J, Geissler C, Parpia B, et al. Antioxidant status and cancer mortality in China. Int J Epidemiol. 1992;21:625-635.

15 Maskarinec G, Williams AE, Inouye JS, et al. A randomized isoflavone intervention among premenopausal women. Cancer Epidemiol Biomarkers Prev. 2002;115:195-201.

16 White E, Shannon JS, Patterson RE. Relationship between vitamin and calcium supplement use and colon cancer. Cancer Epidemiol Biomarkers Prev. 1997;6:769-774.

17 Macready N. Vitamins associated with lower colon-cancer risk. Lancet. 1997;350:1452.

18 Losonczy KG, Harris TB, Havlik RJ. Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the Established Populations for Epidemiologic Studies of the Elderly. Am J Clin Nutr. 1996;64:190-196.

19 Bostick RM, Potter JD, McKenzie DR, et al. Reduced risk of colon cancer with high intake of vitamin E: the Iowa Women's Health Study. Cancer Res. 1993;53:4230-4237.

20 Giovannucci E, Stampfer MJ, Colditz GA, et al. Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med. 1998;129:517-524.

21 Malila N, Virtamo J, Virtanen M, et al. The effect of alpha-tocopherol and beta-carotene supplementation on colorectal adenomas in middle-aged male smokers. Cancer Epidemiol Biomarkers Prev. 1999;8:489-493.

22 Lu LJW, Anderson KE, Grady JJ, et al. Effects of soya consumption for one month on steroid hormones in premenopausal women: implications for breast cancer risk reduction. Cancer Epidemiol Biomarkers Prev. 1996;5:63-70.

23 Greenberg ER, Baron JA, Tosteson TD, et al. A clinical trial of antioxidant vitamins to prevent colorectal adenoma. N Engl J Med. 1994;331:141-147.

24 Woodson K, Tangrea JA, Barrett MJ, et al. Serum alpha-tocopherol and subsequent risk of lung cancer among male smokers. J Natl Cancer Inst. 1999;91:1738-1743.

29 National Research Council Staff. Diet and Health: Implications for Reducing Chronic Disease Risk. Washington, DC: National Academy of Education; 1989:376-379.

30 Clark LC, Combs GF Jr, Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: a randomized controlled trial. Nutritional Prevention of Cancer Study. JAMA. 1996;276:1957-1963.

36 Fleischauer AT, Poole C, Arab L. Garlic consumption and cancer prevention: meta-analyses of colorectal and stomach cancers. Am J Clin Nutr. 2000;72:1047-1052.

37 Agarwal KC. Therapeutic actions of garlic constituents. Med Res Rev. 1996;16:111-124.

38 Dausch JG, Nixon DW. Garlic: a review of its relationship to malignant disease. Prev Med. 1990;19:346-361.

39 Dorant E, van den Brandt PA, Goldbohm RA, et al. Garlic and its significance for the prevention of cancer in humans: a critical view. Br J Cancer. 1993;67:424-429.

40 Lau BH, Tadi PP, Tosk JM. Allium sativum (garlic) and cancer prevention. Nutr Res. 1990;10:937-948.

41 Steinmetz KA, Kushi LH, Bostick RM, et al. Vegetables, fruit, and colon cancer in the Iowa Women's Health Study. Am J Epidemiol. 1994;139:1-15.

42 You WC, Blot WJ, Chang YS, et al. Allium vegetables and reduced risk of stomach cancer. J Natl Cancer Inst. 1989;81:162-164.

43 Ernst E. Can Allium vegetables prevent cancer? Phytomedicine. 1997;4:79-83.

44 Kumar NB, Cantor A, Allen K, et al. The specific role of isoflavones on estrogen metabolism in premenopausal women. Cancer. 2002;94:1166-1174.

45 Sumiyoshi H. New pharmacological activities of garlic and its constituents [in Japanese; English abstract]. Nippon Yakurigaku Zasshi. 1997;110(suppl 1):93P-97P.

46 Michaud DS, Pietinen P, Taylor PR, et al. Intakes of fruits and vegetables, carotenoids and vitamins A, E, C in relation to the risk of bladder cancer in the ATBC cohort study. Br J Cancer. 2002;87:960-965.

47 Popov I, Blumstein A, Lewin G. Antioxidant effects of aqueous garlic extract: 1st communication: direct detection using the photochemiluminescence. Arzneimittelforschung. 1994;44:602-604.

48 Torok B, Belagyi J, Rietz B, et al. Effectiveness of garlic on the radical activity in radical generating systems. Arzneimittelforschung. 1994;44:608-611.

49 Das T, Roychoudhury A, Sharma A, et al. Modification of clastogenicity of three known clastogens by garlic extract in mice in vivo. Environ Mol Mutagen. 1993;21:383-388.

50 Ip C, Lisk DJ. Efficacy of cancer prevention by high-selenium garlic is primarily dependent on the action of selenium. Carcinogenesis. 1995;16:2649-2652.

51 Malila N, Taylor PR, Virtanen MJ, et al. Effects of alpha-tocopherol and beta-carotene supplementation on gastric cancer incidence in male smokers (ATBC Study, Finland). Cancer Causes Control. 2002;13:617-623.

52 Virtamo J, Edwards BK, Virtanen M, et al. Effects of supplemental alpha-tocopherol and beta-carotene on urinary tracct cancer: incidence and mortality in a controlled trial (Finland). Cancer Causes Control. 2000;11:933-939.

53 Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:23-33.

54 Reid ME, Duffield-Lillico AJ, Garland L, et al. Selenium supplementation and lung cancer incidence: an update of the nutritional prevention of cancer trial. Cancer Epidemiol Biomarkers Prev. 2002;11:1285-1291.

55 Steinmetz KA, Potter JD. Vegetables, fruit, and cancer prevention: a review. J Am Diet Assoc. 1996;96:1027-1039.

56 Ziegler RG. A review of epidemiologic evidence that carotenoids reduce the risk of cancer. J Nutr. 1989;119:116-122.

57 Flagg EW, Coates RJ, Greenberg RS. Epidemiologic studies of antioxidants and cancer in humans. J Am Coll Nutr. 1995;14:419-427.

58 Vena JE, Graham S, Freudenheim J, et al. Diet in the epidemiology of bladder cancer in western New York. Nutr Cancer. 1992;18:255-264.

59 Rock CL, Saxe GA, Ruffin MT IV, et al. Carotenoids, vitamin A, and estrogen receptor status in breast cancer. Nutr Cancer. 1996;25:281-296.

60 Allred CD, Allred KF, Ju YH, et al. Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner. Cancer Res. 2001;61:5045-5050.

61 Ju YH, Allred CD, Allred KF, et al. Physiological concentrations of dietary genistein dose-dependently stimulate growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in athymic nude mice. J Nutr. 2001;131:2957-2962.

62 Santamaria L, Bianchi-Santamaria A. Carotenoids in cancer chemoprevention and therapeutic interventions. J Nutr Sci Vitaminol (Tokyo). 1992;Spec No:321-326.

63 Allred CD, Ju YH, Allred KF, et al. Dietary genistin stimulates growth of estrogen-dependent breast cancer tumors similar to that observed with genistein. Carcinogenesis. 2001;22:1667-1673.

64 Omenn GS, Goodman GE, Thornquist MD, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med. 1996;334:1150-1155.

65 Hargreaves DF, Potten CS, Harding C, et al. Two-week dietary soy supplementation has an estrogenic effect on normal premenopausal breast. J Clin Endocrinol Metab. 1999;84:4017-4024.

66 Frieling UM, Schaumberg DA, Kupper TS, et al. A randomized, 12-year primary-prevention trial of beta carotene supplementation for nonmelanoma skin cancer in the Physicians' Health Study. Arch Dermatol. 2000;136:179-184.

67 Lee IM, Cook NR, Manson JE, et al. Beta-carotene supplementation and incidence of cancer and cardiovascular disease: the Women's Health Study. J Natl Cancer Inst. 1999;91:2102-2106.

68 Michaud DS, Feskanich D, Rimm EB, et al. Intake of specific carotenoids and risk of lung cancer in 2 prospective US cohorts. Am J Clin Nutr. 2000;72:990-997.

69 White WS, Stacewicz-Sapuntzakis M, Erdman JW Jr, et al. Pharmacokinetics of beta-carotene and canthaxanthin after ingestion of individual and combined doses by human subjects. J Am Coll Nutr. 1994;13:665-671.

70 Franceschi S, Bidoli E, La Vecchia C, et al. Tomatoes and risk of digestive-tract cancers. Int J Cancer. 1994;59:181-184.

71 Giovannucci E, Ascherio A, Rimm EB, et al. Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl Cancer Inst. 1995;87:1767-1776.

72 Clinton SK, Emenshiser C, Schwartz SJ, et al. cis-trans Lycopene isomers, carotenoids, and retinol in the human prostate. Cancer Epidemiol Biomarkers Prev. 1996;5:823-833.

73 Gann PH, Ma J, Giovannucci E, et al. Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective study. Cancer Res. 1999;59:1225-1230.

74 Gionvannucci E. Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiological literature. J Natl Cancer Inst. 1999;91:317-331.

75 Messina M, Gardner C, Barnes S. Gaining insight into the health effects of soy but a long way still to go: commentary on the fourth International Symposium on the Role of Soy in Preventing and Treating Chronic Disease. J Nutr. 2002;132:547S-551S.

76 Cohen M, Bhagavan HN. Ascorbic acid and gastrointestinal cancer. J Am Coll Nutr. 1995;14:565-578.

77 Ocke MC, Kromhout D, Menotti A, et al. Average intake of anti-oxidant (pro) vitamins and subsequent cancer mortality in the 16 cohorts of the Seven Countries Study. Int J Cancer. 1995;61:480-484.

78 Kromhout D, Bueno-de-Mesquita HB. Antioxidant vitamins and stomach cancer: the role of ecologic studies. Cancer Lett. 1997;114:333-334.

79 Shibata A, Paganini-Hill A, Ross RK, et al. Intake of vegetables, fruits, beta-carotene, vitamin C and vitamin supplements and cancer incidence among the elderly: a prospective study. Br J Cancer. 1992;66:673-679.

80 Manthey JA, Grohmann K, Guthrie N. Biological properties of citrus flavonoids pertaining to cancer and inflammation. Curr Med Chem. 2001;8:135-153.

81 Truswell AS. Meat consumption and colorectal cancer: critique of Norat and Riboli's review. Nutr Rev. 2001;59:375-377.

82 Duncan AM, Underhill KEW, Xu X, et al. Modest hormonal effects of soy isoflavones in postmenopausal women. J Clin Endocrinol Metab. 1999;84:3479-3484.

83 Block G. Epidemiologic evidence regarding vitamin C and cancer. Am J Clin Nutr. 1991;54(suppl 6):1310S-1314S.

84 Khaw KT, Bingham S, Welch A, et al. Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. Lancet. 2001;357:657-663.

85 Daviglus ML, Dyer AR, Persky V, et al. Dietary beta-carotene, vitamin C, and risk of prostate cancer: Results from the Western Electric Study. Epidemiology. 1996;7:472-477.

86 Bruemmer B, White E, Vaughan TL, et al. Nutrient intake in relation to bladder cancer among middle-aged men and women. Am J Epidemiol . 1996;144:485-495.

87 O'Toole P, Lombard M. Vitamin C and gastric cancer: supplements for some or fruit for all. Gut. 1996;39:345-347.

88 Rapola JM, Virtamo J, Haukka JK, et al. Effect of vitamin E and beta carotene on the incidence of angina pectoris. JAMA. 1996;275:693-698.

89 Kushi LH, Fee RM, Sellers TA, et al. Intake of vitamins A, C, and E and postmenopausal breast cancer: the Iowa Women's Health Study. Am J Epidemiol. 1996;144:165-174.

90 Hunter DJ, Manson JE, Colditz GA, et al. A prospective study of the intake of vitamins C, E, and A and the risk of breast cancer. N Engl J Med. 1993;329:234-240.

91 Katiyar SK, Mukhtar H. Tea antioxidants in cancer chemoprevention. J Cell Biochem Suppl. 1997;27:59-67.

92 Stoner GD, Mukhtar H. Polyphenols as cancer chemopreventive agents. J Cell BiochemSuppl. 1995;22:169-180.

93 Wang ZY, Huang MT, Lou YR, et al. Inhibitory effects of black tea, green tea, decaffeinated black tea, and decaffeinated green tea on ultraviolet B light-induced skin carcinogenesis in 7,12-dimethylbenz[ a ] anthracene-initiated SKH-1 mice. Cancer Res. 1994;54:3428-3435.

94 McCord H. More good news in tea leaves. Prevention. 1995;47:51.

95 Yang CS, Wang ZY. Tea and cancer. J Natl Cancer Inst. 1993;85:1038-1049.

96 Imai K, Suga K, Nakachi K, et al. Cancer-preventive effects of drinking green tea among a Japanese population. Prev Med. 1997;26:769-775.

97 Ji BT, Chow WH, Hsing AW, et al. Green tea consumption and the risk of pancreatic and colorectal cancers. Int J Cancer. 1997;70:255-258.

98 Yu GP, Hsieh CC, Wang LY, et al. Green-tea consumption and risk of stomach cancer: a population-based case-control study in Shanghai, China. Cancer Causes Control. 1995;6:532-538.

99 Tsubono Y, Nishino Y, Komatsu S, et al. Green tea and the risk of gastric cancer in Japan. N Engl J Med. 2001;344:632-666.

100 Galanis DJ, Kolonel LN, Lee J, et al. Intakes of selected foods and beverages and the incidence of gastric cancer among the Japanese residents of Hawaii: a prospective study. Int J Epidemiol. 1998;27:173-180.

101 Omenn GS. Micronutirents (viamins and minerals) as cancer-preventive agents. IARC Sci Publ. 1996;139:33-45.

102 Katiyar SK, Ahmad N, Mukhtar H. Green tea and skin. Arch Dermatol. 2000;136:989-994.

103 Komori A, Yatsunami J, Okabe S, et al. Anticarcinogenic activity of green tea polyphenols. Jpn J Clin Oncol. 1993;23:186-190.

104 Cao Y, Cao R. Angiogenesis inhibited by drinking tea [letter]. Nature. 1999;398:381.

105 Messina MJ, Persky V, Setchell KD, et al. Soy intake and cancer risks: a review of the in vitro and in vivo data. Nutr Cancer. 1994;21:113-131.

106 Adlercreutz H, Mazur W. Phyto-oestrogens and western diseases. Ann Med. 1997;29:95-120.

107 Stoll BA. Eating to beat breast cancer: potential role for soy supplements. Ann Oncol. 1997;8:223-225.

108 Day NE. Phyto-estrogens and hormonally dependent cancers. Pathol Biol. 1994;42:1090.

109 Barnes S, Peterson TG, Coward L. Rationale for the use of genistein-containing soy matrices in chemoprevention trials for breast and prostate cancer. J Cell Biochem Suppl. 1995;22:181-187.

110 Ingram D, Sanders K, Kolybaba M, et al. Case-control study of phyto-oestrogens and breast cancer. Lancet. 1997;350:990-994.

111 Goodman MT, Wilkins LR, Hankin JH, et al. Association of soy and fiber consumption with the risk of endometrial cancer. Am J Epidemiol. 1997;146:294-306.

112 LycoRed Natural Products Industries Ltd. New research shows combination of tomato phytonutrients effectively combats breast cancer [press release]. February 2000.

113 Day NE. Phyto-estrogens and hormonally dependent cancers. Pathol Biol. 1994;42:1090.

114 Castellsague X, Munoz N, De Stefani E, et al. Influence of maté drinking, hot beverages and diet on esophageal cancer risk in South America. Int J Cancer. 2000;88:658-664.

120 Butterworth CE Jr. Effect of folate on cervical cancer: synergism among risk factors. Ann N Y Acad Sci. 1992;669:293-299.

121 Kim YI, Mason JB. Folate, epithelial dysplasia, and colon cancer. Proc Assoc Am Physicians. 1995;107:218-227.

122 Tseng M, Murray SC, Kupper LL, et al. Micronutrients and the risk of colorectal adenomas. Am J Epidemiol. 1996;144:1005-1014.

123 Heimburger DC. Localized deficiencies of folic acid in aerodigestive tissues. Ann N Y Acad Sci. 1992;669:87-96.

124 Zhang S, Hunter DJ, Hankinson SE, et al. A prospective study of folate intake and the risk of breast cancer. JAMA. 1999;281:1632-1637.

125 Stolzenberg-Solomon RZ, Pietinen P, Barrett MJ, et al. Dietary and other methyl-group availability factors and pancreatic cancer risk in a cohort of male smokers. Am J Epidemiol. 2001;153:680-687.

126 Cramer DW, Kuper H, Harlow BL, et al. Carotenoids, antioxidants and ovarian cancer risk in pre- and postmenopausal women. Int J Cancer. 2001;94:128-134.

127 Giovannucci E, Stampfer MJ, Colditz GA, et al. Folate, methionine, and alcohol intake and risk of colorectal adenoma. J Natl Cancer Inst. 1993;85:875-884.

128 Schatzkin A. Trials on dietary prevention of cancer: polyps and vegetables. Presented at: European Conference on Nutrition & Cancer; June 21-24, 2001; Lyon, France.

129 Baron JA, Sandler RS, Haile RW, et al. Folate intake, alcohol consumption, cigarette smoking, and risk of colorectal adenomas. J Natl Cancer Inst. 1998;90:57-62.

130 Kearney J, Giovannucci E, Rimm EB, et al. Calcium, vitamin D, and dairy foods and the occurrence of colon cancer in men. Am J Epidemiol. 1996;143:907-917.

131 Baron JA, Beach M, Mandel JS, et al. Calcium supplements for the prevention of colorectal adenomas. N Engl J Med. 1999;340:101-107.

132 Hyman J, Baron JA, Dain BJ, et al. Dietary and supplemental calcium and the recurrence of colorectal adenomas. Cancer Epidemiol Biomarkers Prev. 1998;7:291-295.

133 Lipkin M, Newmark H. Effect of added dietary calcium on colonic epithelial-cell proliferation in subjects at high risk for familial colonic cancer. N Engl J Med. 1985;313:1381-1384.

134 Pence BC. Role of calcium in colon cancer prevention: experimental and clinical studies. Mutat Res. 1993;290:87-95.

135 Bostick RM, Fosdick L, Wood JR, et al. Calcium and colorectal epithelial cell proliferation in sporadic adenoma patients: a randomized, double-blinded, placebo-controlled clinical trial. J Natl Cancer Inst. 1995;87:1307-1315.

136 Baron JA, Tosteson TD, Wargovich MJ, et al. Calcium supplementation and rectal mucosal proliferation: a randomized controlled trial. J Natl Cancer Inst. 1995;87:1303-1307.

137 Holt PR, Atillasoy EO, Gilman J, et al. Modulation of abnormal colonic epithelial cell proliferation and differentiation by low-fat dairy foods: a randomized controlled trial. JAMA. 1998;280:1074-1079.

138 Lapre JA, De Vries HT, Termont DS, et al. Mechanism of the protective effect of supplemental dietary calcium on cytolytic activity of fecal water. Cancer Res. 1993;53:248-253.

139 Martinez ME, Willett WC. Calcium, vitamin D, and colorectal cancer: a review of the epidemiologic evidence. Cancer Epidemiol Biomarkers Prev. 1998;7:163-168.

140 Garland FC, Garland CF, Gorham ED, et al. Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Prev Med. 1990; 19:614-622.

141 Key SW, Marble M. Studies link sun exposure to protection against cancer. Cancer Weekly Plus. 1997;5-6.

142 Martinez ME, Giovannucci EL, Colditz GA, et al. Calcium, vitamin D, and the occurrence of colorectal cancer among women. J Natl Cancer Inst. 1996;88:1375-1382.

143 Norat T, Van Bakel M, Riboli E. Fruit and vegetable consumption and risk of cancer of the digestive tract: meta-analysis of published case-control and cohort studies. Presented at: European Conference on Nutrition & Cancer; June 21-24, 2001; Lyon, France.

144 James SY, Mackay AG, Colston KW. Effects of 1,25 dihydroxyvitamin D 3 and its analogues on induction of apoptosis in breast cancer cells. J Steroid Biochem Mol Biol. 1996;58:395-401.

145 Taylor JA, Hirvonen A, Watson M, et al. Association of prostate cancer with vitamin D receptor gene polymorphism. Cancer Res. 1996;56:4108-4110.

146 Douglas WC. Vitamin D scores again. Second Opin. 1997;7:4-5.

147 Fuller KE, Casparian JM. Vitamin D: balancing cutaneous and systematic considerations. South Med J. 2001;94:58-64.

148 Gilchrest BA, Eller MS, Geller AC, et al. The pathogenesis of melanoma induced by ultraviolet radiation. N Engl J Med. 1999;340:1341-1348.

149 Studzinski GP, Moore DC. Sunlight—can it prevent as well as cause cancer? Cancer Res. 1995;55:4014-4022.

150 Blutt SE, Weigel NL. Vitamin D and prostate cancer. Proc Soc Exp Biol Med. 1999;221:89-98.

151 Vandewalle B, Hornez L, Wattez N, et al. Vitamin-D 3 derivatives and breast-tumor cell growth: effect on intracellular calcium and apoptosis. Int J Cancer. 1995;61:806-811.

152 Hofer H, Ho GM, Peterlik M, et al. Biological effects of 1alpha-hydroxy- and 1beta-(hydroxymethyl)-vitamin D compounds relevant for potential colorectal cancer therapy. J Pharmacol Exp Ther. 1999;291:450-455.

153 Tong WM, Kallay E, Hofer H, et al. Growth regulation of human colon cancer cells by epidermal growth factor and 1,25-dihydroxyvitamin D3 is mediated by mutual modulation of receptor expression. Eur J Cancer. 1998;34:2119-2125.

154 Ekman P. Genetic and environmental factors in prostate cancer genesis: identifying high-risk cohorts. Eur Urol. 1999;35:362-369.

155 Peehl DM. Vitamin D and prostate cancer risk. Eur Urol. 1999;35:392-394.

156 Hanchette CL, Schwartz GG. Geographic patterns of prostate cancer mortality. Evidence for a protective effect of ultraviolet radiation. Cancer. 1992;70:2861-2869.

157 Moffatt KA, Johannes WU, Miller GJ. 1Alpha,25dihydroxyvitamin D3 and platinum drugs act synergistically to inhibit the growth of prostate cancer cell lines. Clin Cancer Res. 1999;5:695-703.

158 Danielsson C, Torma H, Vahlquist A, et al. Positive and negative interaction of 1,25-dihydroxyvitamin D3 and the retinoid CD437 in the induction of human melanoma cell apoptosis. Int J Cancer. 1999;81:467-470.

159 Evans SR, Houghton AM, Schumaker L, et al. Vitamin D receptor and growth inhibition by 1,25-dihydroxyvitamin D3 in human malignant melanoma cell lines. J Surg Res. 1996;61:127-133.

160 Trock B, Lanza E, and Greenwald P. Dietary fiber, vegetables, and colon cancer: critical review and meta-analyses of the epidemiologic evidence. J Natl Cancer Inst. 1990;82:650-661.

161 Howe GR, Benito E, Castelleto R, et al. Dietary intake of fiber and decreased risk of cancers of the colon and rectum: evidence from the combined analysis of 13 case-control studies. J Natl Cancer Inst. 1992;84:1887-1896.

162 Platz EA, Giovannucci E, Rimm EB, et al. Dietary fiber and distal colorectal adenoma in men. Cancer Epidemiol Biomarkers Prev. 1997;6:661-670.

163 Bingham S, Day NE, Luben R, et al. Plant polysaccharides, meat and colorectal cancer. Presented at: European Conference on Nutrition & Cancer; June 21-24, 2001; Lyon, France.

164 Miller AB, for the EPIC group. Vegetables and fruits and lung cancer. Presented at: European Conference on Nutrition & Cancer; June 21-24, 2001; Lyon, France.

165 Giovannucci E, Rimm EB, Stampfer MJ, et al. Intake of fat, meat, and fiber in relation to risk of colon cancer in men. Cancer Res. 1994;54:2390-2397.

166 Fuchs CS, Giovannucci EL, Colditz GA, et al. Dietary fiber and the risk of colorectal cancer and adenoma in women. N Engl J Med. 1999;340:169-176.

167 MacLennan R, Macrae F, Bain C, et al. Randomized trial of intake of fat, fiber, and beta carotene to prevent colorectal adenomas. The Australian Polyp Prevention Project. J Natl Cancer Inst. 1995;87:1760-1766.

168 McKeown-Eyssen GE, Bright-See E, Bruce WR, et al. A randomized trial of low fat high fibre diet in the recurrence of colorectal polyps. Toronto Polyp Prevention Group. J Clin Epidemiol. 1994;47:525-536.

169 Schatzkin A, Lanza E, Corle D, et al. Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group. N Engl J Med. 2000;342:1149-1155.

170 Alberts DS, Martinez ME, Roe DJ, et al. Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. Phoenix Colon Cancer Prevention Physicians' Network. N Engl J Med. 2000;342:1156-1162.

171 Gonzales CA, for the EPIC group. Vegetables, fruit and cereals consumption and the gastric cancer risk. Presented at: European Conference on Nutrition & Cancer; June 21-24, 2001; Lyon, France.

172 Adlercreutz H, Fotsis T, Heikkinen R, et al. Excretion of the lignans enterolactone and enterodiol and of equol in omnivorous and vegetarian postmenopausal women and in women with breast cancer. Lancet. 1982;2:1295-1299.

173 Thompson LU. Experimental studies on lignans and cancer. Baillieres Clin Endocrinol Metab. 1998;12:691-705.

174 Thompson LU, Rickard SE, Orcheson LJ, et al. Flaxseed and its lignan and oil components reduce mammary tumor growth at a late stage of carcinogenesis. Carcinogenesis. 1996;17:1373-1376.

175 Bougnoux P, Koscielny S, Chajes V, et al. Alpha-linolenic acid content of adipose breast tissue: a host determinant of the risk of early metastasis in breast cancer. Br J Cancer. 1994;70:330-334.

176 Rose DP. Dietary fatty acids and cancer. Am J Clin Nutr. 1997;66(suppl):998S-1003S.

177 Bueno de Mesquita HB, for the EPIC group. Plantfoods and colorectal cancer in the EPIC cohort. Presented at: European Conference on Nutrition & Cancer; June 21-24, 2001; Lyon, France.

178 Serraino M, Thompson LU. The effect of flaxseed supplementation on the initiation and promotional stages of mammary tumorigenesis. Nutr Cancer. 1992;17:153-159.

179 Yan L, Yee JA, Li D, et al. Dietary flaxseed supplementation and experimental metastasis of melanoma cells in mice. Cancer Lett. 1998;124:181-186.

180 Sung MK, Lautens M, Thompson LU. Mammalian lignans inhibit the growth of estrogen-independent human colon tumor cells. Anticancer Res. 1998;18:1405-1408.

181 Yuan YV, et al. Short-term feeding of flaxseed or its lignan has minor influence on in vivo hepatic antioxidant status in young rats. Nutr Res. 1999;19:1233-1243.

182 Bidoli E, La Vecchia C, Talamini R, et al. Micronutrients and ovarian cancer: a case-controlled study in Italy. Presented at: European Conference on Nutrition & Cancer; June 21-24, 2001; Lyon, France.

183 Appleby P, Key T, Burr M, et al. Mortality and fresh fruit consumption. Presented at: European Conference on Nutrition & Cancer; June 21-24, 2001; Lyon, France.

184 Shamsuddin AM, Vucenik I, Cole KE. IP6: a novel anti-cancer agent. Life Sc. 1997;61:343-354.

186 Jang M, Cai L, Udeani GO, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997;275:218-220.

187 ElAttar TM, Virji AS. Modulating effect of resveratrol and quercetin on oral cancer cell growth and proliferation. Anticancer Drugs. 1999;10:187-193.

189 Wojtowicz-Praga S. Clinical potential of matrix metalloprotease inhibitors. Drugs R D (New Zealand). 1999;1:117-129.

190 Dupont E, Savard PE, Jourdain C, et al. Antiangiogenic properties of a novel shark cartilage extract: Potential role in the treatment of psoriasis. J Cutan Med Surg. 1998;2:146-152.

191 Sheu JR, Fu CC, Tsai ML, et al. Effect of U-995, a potent shark cartilage-derived angiogenesis inhibitor, on anti-angiogenesis and anti-tumor activities. Anticancer Res. 1998;18:4435-4441.

192 Davis PF, He Y, Furneaux RH, et al. Inhibition of angiogenesis by oral ingestion of powdered shark cartilage in a rat model. Microvasc Res. 1997;54:178-182.

193 Oikawa T, Ashino-Fuse H, Shimamura M, et al. A novel angiogenic inhibitor derived from Japanese shark cartilage (I). Extraction and estimation of inhibitory activities toward tumor and embryonic angiogenesis. Cancer Lett. 1990;51:181-186.

194 McGuire TR, Kazakoff PW, Hoie EB, et al. Antiproliferative activity of shark cartilage with and without tumor necrosis factor-alpha in human umbilical vein endothelium. Pharmacotherapy. 1996;16:237-244.

195 Lee A, Langer R. Shark cartilage contains inhibitors of tumor angiogenesis. Science. 1983;221:1185-1187.

196 Riviere M, Latreille J, Falardeau P, et al. AE-941 (Neovastat), an inhibitor of angiogenesis: phase I/II cancer clinical trial results. Cancer Invest. 1999;17(suppl 1):16-17.

197 Jamali M-A, Riviere M, Falardeau P, et al. Effect of AE-941 (Neovastat), an angiogenesis inhibitor, in the Lewis lung carcinoma metastatic model, efficacy, toxicity prevention and survival. Clin Invest Med. 1998;(suppl):S16.

198 Riviere M, Falardeau P, Latreille J, et al. Phase I/II lung cancer clinical trial results with AE-941 (Neovastat), an inhibitor of angiogenesis. Clin Invest Med. 1998;(suppl):S14.

199 Riviere M, Alaoui-Jamali M, Falardeau P, et al. Neovastat: an inhibitor of angiogenesis with anti-cancer activity. Presented at: Proceedings of the American Association for Cancer Research Annual Meeting 39; March 28-April 1, 1998; New Orleans, LA.

200 Blasecki J, Alaoui-Jamali M, Wang T, et al. Oral administration of Neovastat inhibits tumor progression in animal models of progressive tumor growth and metastasis. Int J Oncol. 1997;11(suppl):934.

201 Dupont E, Alaoui-Jamali M, Wang T, et al. Angiostatic and antitumoral activity of AE-941 (Neovastat), a molecular fraction derived from shark cartilage. Presented at: Proceedings of the American Association for Cancer Research Annual Meeting 38; April 12-16, 1997; San Diego, CA.

202 Horsman MR, Alsner J, Overgaard J. The effect of shark cartilage extracts on the growth and metastatic spread of the SCCVII carcinoma. Acta Oncol. 1998;37:441-445.

203 Miller DR, Anderson GT, Stark JJ, et al. Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer. J Clin Oncol. 1998;16:3649-3655.

204 Zhang ZF, Winton MI, Rainey C, et al. Boron is associated with decreased risk of human prostate cancer. Presented at: Experimental Biology 2001; March 31-April 4, 2001; Orlando, FL.

205 Kelloff GJ, Crowell JA, Steele VE, et al. Progress in cancer chemoprevention: development of diet-derived chemopreventive agents. J Nutr. 2000;130(suppl):467S-471S.

206 Fahey JW, Zhang Y, Talalay P. Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc Natl Acad Sci USA. 1997;94:10367-10372.

207 Fahey JW, Talalay P. Antioxidant functions of sulforaphane: a potent inducer of Phase II detoxication enzymes. Food Chem Toxicol. 1999;37:973-979.

208 Shertzer HG, Berger ML, Tabor MW. Intervention in free radical mediated hepatotoxicity and lipid peroxidation by indole-3-carbinol. Biochem Pharmacol. 1988;37:333-338.

209 Michnovicz JJ. Increased estrogen 2-hydroxylation in obese women using oral indole-3-carbinol. Int J Obes Relat Metab Disord. 1998;22:227-229.

210 Chen I, Safe S, Bjeldanes L. Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells. Biochem Pharmacol. 1996;51:1069-1076.

211 Bradlow HL, Sepkovic DW, Telang NT, et al. Multifunctional aspects of the action of indole-3-carbinol as an antitumor agent. Ann N Y Acad Sci. 1999;889:204-213.

212 Background information. Indole-3-carbinol (I3C). National Institute of Environmental Health Sciences website. Available at: http://ntp-server.niehs.nih.gov/htdocs/Chem%5FBackground/ExecSumm/Indolecarbinoll . Accessed September 19, 2000.

213 Bailey GS, Hendricks JD, Shelton DW, et al. Enhancement of carcinogenesis by the natural anticarcinogen indole-3-carbinol. J Natl Cancer Inst. 1987;78:931-934.

214 Dashwood RH. Indole-3-carbinol: anticarcinogen or tumor promoter in brassica vegetables? Chem Biol Interact. 1998;110:1-5.

215 Arts IC, Jacobs DR Jr, Folsom AR. Dietary catechins and cancer incidence: the Iowa Women's Health Study. Presented at: European Conference on Nutrition and Cancer; June 21-24, 2001; Lyon, France.

216 Balasubramanian S, Govindasamy S. Inhibitory effect of dietary flavonol quercetin on 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Carcinogenesis. 1996;17:877-879.

217 Cross HJ, Tilby M, Chipman JK, et al. Effect of quercetin on the genotoxic potential of cisplatin. Int J Cancer. 1996;66:404-408.

218 Hoffman R, Graham L, Newlands ES. Enhanced anti-proliferative action of busulphan by quercetin on the human leukaemia cell line K562. Br J Cancer. 1989;59:347-348.

219 Vucenik I, Kalebic T, Tantivejkul K, et al. Novel anticancer function of inositol hexaphosphate: inhibition of human rhabdomyosarcoma in vitro and in vivo.Anticancer Res. 1998;18:1377-1384.

220 Yoshida M, Yamamoto M, Nikaido T. Quercetin arrests human leukemic T-cells in late G 1 phase of the cell cycle. Cancer Res. 1992;52:6676-6681.

221 Ip C, Banni S, Angioni E, et al. Conjugated linoleic acid-enriched butter fat alters mammary gland morphogenesis and reduces cancer risk in rats. J Nutr. 1999;129:2135-2142.

222 Norrish AE, Skeaff CM, Arribas GLB, et al. Prostate cancer risk and consumption of fish oils: a dietary biomarker-based case-control study. Br J Cancer. 1999;81:1238-1242.

223 Estensen RD, Levy M, Kloop SJ, et al. N-acetylcysteine suppression of the proliferative index in the colon of patients with previous adenomatous colonic polyps. Cancer Lett. 1999;147:109-114.

224 Shamsuddin AM, Vucenik I. Mammary tumor inhibition by IP6: a review. Anticancer Res. 1999;19:3671-3674.

225 Wei H, Bowen R, Cai Q, et al. Antioxidant and antipromotional effects of the soybean isoflavone genistein. Proc Soc Exp Biol Med. 1995;208:124-130.

226 Tham DT, Gardner CD, Haskell WL. Clinical review 97: Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab. 1998;83:2223-2235.

227 Konrad L, Muller HH, Lenz C, et al. Antiproliferative effect on human prostate cancer cells by a stinging nettle root ( Urtica dioica ) extract. Planta Med. 2000;66:44-47.

228 Schwartz J, Shklar G, Reid S, et al. Prevention of experimental oral cancer by extracts of Spirulina-Dunaliell a algae. Nutr Cancer. 1988;11:127-134.

229 Mathew B, Sankaranarayanan R, Nair PP, et al. Evaluation of chemoprevention of oral cancer with Spirulina fusiformis.Nutr Cancer. 1995;24:197-202.

230 Mishima T, Murata J, Toyoshima M, et al . Inhibition of tumor invasion and metastasis by calcium spirulan (Ca-SP), a novel sulfated polysaccharide derived from a blue-green alga, Spirulina platensis.Clin Exp Metastasis. 1998;16:541-550.

231 Habib FK, Ross M, Buck AC, et al. In vitro evaluation of the pollen extract, cernitin T-60, in the regulation of prostate cell growth. Br J Urol. 1990;66:393-397.

232 Roberts KP, Iyer RA, Prasad G, et al. Cyclic hydroxamic acid inhibitors of prostate cancer cell growth: selectivity and structure activity relationships. Prostate. 1998;34:92-99.

233 Zhang X, Habib FK, Ross M, et al. Isolation and characterization of a cyclic hydroxamic acid from a pollen extract, which inhibits cancerous cell growth in vitro. J Med Chem. 1995;38:735-738.

234 Chida K, Yamamoto I. Antitumor activity of a crude fucoidan fraction prepared from the roots of kelp ( Laminaria species). Kitasato Arch Exp Med. 1987;60:33-39.

235 Maruyama H, Watanabe K, Yamamoto I. Effect of dietary kelp on lipid peroxidation and glutathione peroxidase activity in livers of rats given breast carcinogen DMBA. Nutr Cancer. 1991;15:221-228.

236 Teas J. The dietary intake of Laminaria , a brown seaweed, and breast cancer prevention. Nutr Cancer. 1983;4:217-222.

237 Funahashi H, Imai T, Tanaka Y, et al. Wakame seaweed suppresses the proliferation of 7,12-dimethylbenz(a)-anthracene-induced mammary tumors in rats. Jpn J Cancer Res. 1999;90:922-927.

238 Shan BE, Yoshida Y, Kuroda E, et al. Immunomodulating activity of seaweed extract on human lymphocytes in vitro.Int J Immunopharmacol. 1999;21:59-70.

239 Ohno Y, Yoshida O, Oishi K, et al. Dietary beta-carotene and cancer of the prostate: a case-control study in Kyoto, Japan. Cancer Res. 1988;48:1331-1336.

240 Rose ML, Cattley RC, Dunn C, et al. Dietary glycine prevents the development of liver tumors caused by the peroxisome proliferator WY-14,643. Carcinogenesis. 1999;20:2075-2081.

241 Rose ML, Madren J, Bunzendahl H, et al. Dietary glycine inhibits the growth of B16 melanoma tumors in mice. Carcinogenesis. 1999;20:793-798.

242 Hancke JL, Burgos RA, Ahumada F. Schisandra chinensis (Turcz.) Baill. Fitoterapia. 1999;70:451-471.

243 Liu J, Xiao P-G. Recent advances in the study of antioxidative effects of Chinese medicinal plants. Phytother Res . 1994;8:445-451.

244 Liu G-T. Pharmacological actions and clinical use of Fructus schizandrae.Chin Med J. 1989;102:740-749.

245 Wattenberg LW. Chemoprevention of pulmonary carcinogenesis by myo-inositol. Anticancer Res. 1999;19:3659-3661.

246 Dong Z, Huang C, Ma WY. PI-3 kinase in signal transduction, cell transformation, and as a target for chemoprevention of cancer. Anticancer Res. 1999;19:3743-3747.

247 Yang GY, Shamsuddin AM. IP6-induced growth inhibition and differentiation of HT-29 human colon cancer cells: involvement of intracellular inositol phosphates. Anticancer Res. 1995;15:2479-2487.

248 Ishikawa T, Nakatsuru Y, Zarkovic M, et al. Inhibition of skin cancer by IP6 in vivo: initiation-promotion model. Anticancer Res. 1999;19:3749-3752.

249 Shamsuddin AM. Metabolism and cellular functions of IP6: a review. Anticancer Res. 1999;19:3733-3736.

250 Duffield-Lillico AJ, Slate EH, Reid ME, et al. Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial. J Natl Cancer Inst. 2003;95:1477-81.

251 Hercberg S, Galan P, Preziosi P, et al. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med. 2004;164:2335-42.

252 NB, Cantor A, Allen K, et al. The specific role of isoflavones in reducing prostate cancer risk. Prostate. 2004;59:141-147.

253 Diculescu M, Ciocirlan M, Ciocirlan M, et al. Folic acid and sulfasalazine for colorectal carcinoma chemoprevention in patients with ulcerative colitis: the old and new evidence. Rom J Gastroenterol. 2004;12:283-286.

254 Grau MV, Baron JA, Sandler RS, et al. Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trial. J Natl Cancer Inst. 2003;95:1765-1771.

255 Wang MY, Su C. Cancer preventive effect of Morina citrifolia (Noni). Ann NY Acad Sci. 2001;952:161-8.

256 Alberts D, Ranger-Moore J, Einspahr J, et al. Safety and efficacy of dose-intensive oral vitamin A in subjects with sun-damaged skin. Clin Cancer Res. 2004;10:1875-1880.

257 Levine N, Moon TE, Cartmel B, et al. Trial of retinol and isotretinoin in skin cancer prevention: a randomized, double-blind, controlled trial. Southwest Skin Cancer Prevention Study Group. Cancer Epidemiol Biomarkers Prev. 1997;6:957-961.

258 Moon TE, Levine N, Cartmel B, et al. Effect of retinol in preventing squamous cell skin cancer in moderate-risk subjects: a randomized, double-blind, controlled trial. Southwest Skin Cancer Prevention Study Group. Cancer Epidemiol Biomarkers Prev. 1997;6:949-956.

259 Habu D, Shiomi S, Tamori A, et al. Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver. JAMA. 2004;292:358-361.

260 van Gils C, Peeters P, Bueno-de-Mesquita H, et al. Consumption of vegetables and fruits and risk of breast cancer. JAMA. 2005;293:183-193.

261 Chao A, Michael J, Thun M, et al. Meat consumption and risk of colorectal cancer. JAMA. 2005;293:172-182.

262 Terry PD, Jain M, Miller AB, et al. Glycemic load, carbohydrate intake, and risk of colorectal cancer in women: a prospective cohort study. J Natl Cancer Inst. 2003;95:914-916.

263 Lonn E, Bosch J, Yusuf S, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA. 2005;293:1338-1347.

264 Lee IM, Cook NR, Gaziano JM, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial. JAMA. 2005;294:56-65.

265 Bairati I, Meyer F, Gelinas M, et al. A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients. J Natl Cancer Inst. 2005;97:481-488.

266 Reid ME, Duffield-Lillico AJ, Sunga A, et al. Selenium supplementation and colorectal adenomas: An analysis of the nutritional prevention of cancer trial. Int J Cancer. 2005 Oct 10. [Epub ahead of print]

267 Mohanty NK, Saxena S, Singh UP, et al. Lycopene as a chemopreventive agent in the treatment of high-grade prostate intraepithelial neoplasia. Urol Oncol. 2005;23:383-385.

268 Kucuk O, Sarkar FH, Sakr W, et al. Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy. Cancer Epidemiol Biomarkers Prev. 2001;10:861-868.

269 LycoRed Natural Products Industries Ltd. New research shows combination of tomato phytonutrients effectively combats breast cancer [press release]. February 2000.

270 Holt PR, Bresalier RS, Ma CK, et al. Calcium plus vitamin D alters preneoplastic features of colorectal adenomas and rectal mucosa. Cancer. 2005 Dec 13. [Epub ahead of print]

271 Sandler RS. Calcium supplements to prevent colorectal adenomas. Am J Gastroenterol. 2005;100:395-396.

272 Wactawski-Wende J, Kotchen JM, Anderson GL, et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med. 2006;354:684-696.

273 Mitrou PN, Albanes D, Pietinen P, et al. Poster session: Intakes of calcium, dairy products, and prostate cancer risk in the ATBC Study. NIH Research Festival; Oct. 18, 2005.

274 Giovannucci E, Rimm EB, Wolk A, et al. Calcium and fructose intake in relation to risk of prostate cancer. Cancer Res. 1998;58:442-447.

275 Giovannucci E, Liu Y, Rimm EB, et al. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst. 2006;98:451-459.

276 Hooper L, Thompson RL, Harrison RA, et al. Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ. 2006 Mar 24. [Epub ahead of print]

277 Beresford SA, Johnson KC, Ritenbaugh C, et al. Low-fat dietary pattern and risk of colorectal cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006;295:643-654.

278 Prentice RL, Caan B, Chlebowski RT, et al. Low-fat dietary pattern and risk of invasive breast cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006;295:629-642.

279 Hercberg S, Czernichow S, Galan P. Antioxidant vitamins and minerals in prevention of cancers: lessons from the SU.VI.MAX study. Br J Nutr. 2006;96(suppl 1):S28-S30.

280 Buring JE. Aspirin prevents stroke but not MI in women; vitamin E has no effect on CV disease or cancer. Cleve Clin J Med. 2006;73:863-870.

281 Barber NJ, Zhang X, Zhu G, et al. Lycopene inhibits DNA synthesis in primary prostate epithelial cells in vitro and its administration is associated with a reduced prostate-specific antigen velocity in a phase II clinical study. Prostate Cancer Prostatic Dis. 2006 Sep 19. [Epub ahead of print]

282 Samad AK, Taylor RS, Marshall T, et al. A meta-analysis of the association of physical activity with reduced risk of colorectal cancer. Colorectal Dis. 2005;7:204-213.

283 Grau MV, Baron JA, Sandler RS, et al. Prolonged effect of calcium supplementation on risk of colorectal adenomas in a randomized trial. J Natl Cancer Inst. 2007;99:129-136.

284 Plummer M, Vivas J, Lopez G, et al. Chemoprevention of precancerous gastric lesions with antioxidant vitamin supplementation: a randomized trial in a high-risk population. J Natl Cancer Inst. 2007;99:137-146.

285 Dreno B, Euvrard S, Frances C, et al. Effect of selenium intake on the prevention of cutaneous epithelial lesions in organ transplant recipients. Eur J Dermatol. 2007;17:140-145.

286 Armstrong WB, Kennedy AR, Wan XS, et al. Clinical modulation of oral leukoplakia and protease activity by Bowman-Birk inhibitor concentrate in a phase IIa chemoprevention trial. Clin Cancer Res. 2000;6:4684-4691.

287 Meyskens FL. Development of Bowman-Birk inhibitor for chemoprevention of oral head and neck cancer. Ann N Y Acad Sci. 2001;952:116-123.

288 Kennedy AR, Billings PC, Wan XS, et al. Effects of Bowman-Birk inhibitor on rat colon carcinogenesis. Nutr Cancer. 2002;43:174-186.

289 Armstrong WB, Wan XS, Kennedy AR, et al. Development of the Bowman-Birk inhibitor for oral cancer chemoprevention and analysis of Neu immunohistochemical staining intensity with Bowman-Birk inhibitor concentrate treatment. Laryngoscope. 2003;113:1687-1702.

290 Wright ME, Weinstein SJ, Lawson KA, et al. Supplemental and dietary vitamin E intakes and risk of prostate cancer in a large prospective study. Cancer Epidemiol Biomarkers Prev. 2007;16:1128-1135.

291 Cole BF, Baron JA, Sandler RS, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA. 2007;297:2351-2359.

292 Lappe JM, Travers-Gustafson D, Davies KM, et al. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007;85:1586-1591.

293 Nakaya M, Onda H, Sasaki K, et al. Effect of royal jelly on bisphenol A-induced proliferation of human breast cancer cells. Biosci Biotechnol Biochem. 2007;71:253-255.

294 Lanza E, Yu B, Murphy G, et al. The polyp prevention trial continued follow-up study: no effect of a low-fat, high-fiber, high-fruit, and -vegetable diet on adenoma recurrence eight years after randomization. Cancer Epidemiol Biomarkers Prev. 2007;16:1745-1752.

295 Ngo SN, Williams DB, Cobiac L, et al. Does garlic reduce risk of colorectal cancer? A systematic review. J Nutr. 2007;137:2264-2269.

296 Tanaka S, Haruma K, Kunihiro M, et al. Effects of aged garlic extract (AGE) on colorectal adenomas: a double-blinded study. Hiroshima J Med Sci. 2004;53:39-45.

297 Hamilton-Reeves JM, Rebello SA, Thomas W, et al. Soy protein isolate increases urinary estrogens and the ratio of 2:16 alpha-hydroxyestrone in men at high risk of prostate cancer. J Nutr. 2007;137:2258-2263.

298 Goldin BR, Brauner E, Adlercreutz H, et al. Hormonal response to diets high in soy or animal protein without and with isoflavones in moderately hypercholesterolemic subjects. Nutr Cancer. 2005;51:1-6.

299 Adams KF, Chen C, Newton KM, et al. Soy isoflavones do not modulate prostate-specific antigen concentrations in older men in a randomized controlled trial. Cancer Epidemiol Biomarkers Prev. 2004;13:644-648.

300 Prentice RL, Thomson CA, Caan B, et al. Low-fat dietary pattern and cancer incidence in the women's health initiative dietary modification randomized controlled trial. J Natl Cancer Inst. 2007 Oct 9. [Epub ahead of print]

301 Bardia A, Tleyjeh IM, Cerhan JR, et al. Efficacy of antioxidant supplementation in reducing primary cancer incidence and mortality: systematic review and meta-analysis. Mayo Clin Proc. 2008;83:23-34.

302 Weingarten M, Zalmanovici A, Yaphe J. Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps. Cochrane Database Syst Rev. 2008;CD003548.

303 Michels KB, Willett WC. The Women's Health Initiative Randomized Controlled Dietary Modification Trial: a post-mortem. Breast Cancer Res Treat. 2008 Mar 30. [Epub ahead of print]

304 Bardia A, Tleyjeh IM, Cerhan JR, et al. Efficacy of antioxidant supplementation in reducing primary cancer incidence and mortality: systematic review and meta-analysis. Mayo Clin Proc. 2008;83:23-34.

305 Tanvetyanon T, Bepler G. Beta-carotene in multivitamins and the possible risk of lung cancer among smokers versus former smokers: a meta-analysis and evaluation of national brands. Cancer. 2008 Apr 21.

306 Hall MN, Chavarro JE, Lee IM, et al. A 22-year prospective study of fish, n-3 fatty acid intake, and colorectal cancer risk in men. Cancer Epidemiol Biomarkers Prev. 2008;17:1136-1143.

307 Bobe G, Sansbury LB, Albert PS, et al. Dietary flavonoids and colorectal adenoma recurrence in the polyp prevention trial. Cancer Epidemiol Biomarkers Prev. 2008;17:1344-1353.

308 Bjelakovic G, Nikolova D, Simonetti RG, et al. Systematic review and meta-analysis: primary and secondary prevention of gastrointestinal cancers with antioxidant supplements. Aliment Pharmacol Ther. 2008 Jun 30.

309 Jaszewski R, Misra S, Tobi M, et al. Folic acid supplementation inhibits recurrence of colorectal adenomas: A randomized chemoprevention trial. World J Gastroenterol. 2008;14:4492-4498.

310 Peters U, Littman AJ, Kristal AR, Patterson RE, Potter JD, White E. Vitamin E and selenium supplementation and risk of prostate cancer in the Vitamins and lifestyle (VITAL) study cohort. Cancer Causes Control. 2008;19:75-87.

311 Liu J, Xing J, Fei Y. Green tea ( Camellia sinensis ) and cancer prevention: a systematic review of randomized trials and epidemiological studies. Chin Med. 2008;3:12.

312 Myung SK, Bae WK, Oh SM, et al. Green tea consumption and risk of stomach cancer: a meta-analysis of epidemiologic studies. Int J Cancer. 2009;124:670-677.

313 Shimizu M, Fukutomi Y, Ninomiya M, et al. Green tea extracts for the prevention of metachronous colorectal adenomas: a pilot study. Cancer Epidemiol Biomarkers Prev. 2008;17:3020-3025.

314 Wei MY, Garland CF, Gorham ED, et al. Vitamin D and prevention of colorectal adenoma: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2008;17:2958-2969.

315 Zhang SM, Cook NR, Albert CM, et al. Effect of combined folic acid, vitamin B6, and vitamin B12 on cancer risk in women: a randomized trial. JAMA. 2008;300:2012-2021.

316 Chlebowski RT, Johnson KC, Kooperberg C, et al. Calcium plus vitamin D supplementation and the risk of breast cancer. J Natl Cancer Inst. 2008;100:1581-1591.

317 Ogunleye AA, Xue F, Michels KB. Green tea consumption and breast cancer risk or recurrence: a meta-analysis. Breast Cancer Res Treat. 2010 Jan;119(2):477.

318 Aune D, Chan DS, Lau R, et al. Dietary fibre, whole grains, and risk of colorectal cancer: systematic review and dose-response meta-analysis of prospective studies. BMJ. 2011;343:d6617.

319 Myung SK, Ju W, Kim SC, Kim H; Korean Meta-analysis (KORMA) Study Group. Vitamin or antioxidant intake (or serum level) and risk of cervical neoplasm: a meta-analysis. BJOG. 2011;118(11):1285-1291.

320 Andreeva VA, Touvier M, Kesse-Guyot E, et al. B Vitamin and/or ω-3 Fatty acid supplementation and cancer: ancillary findings from the supplementation with folate, vitamins B6 and B12, and/or omega-3 fatty acids (SU.FOL.OM3) randomized trial. Arch Intern Med. 2012 Feb 13. [Epub ahead of print]

321 Aune D, Lau R, Chan DS, et al. Nonlinear reduction in risk for colorectal cancer by fruit and vegetable intake based on meta-analysis of prospective studies. Gastroenterology. 2011;141(1):106-118.

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