Breast Cancer

Breast cancer is the most common cancer in women both in developed and developing countries, comprising 16 percent of all female cancers. Since 1970, scientists have suggested that there may be a link between excess body weight and breast cancer. According to the National Cancer Institute (NCI), weight gain during adulthood is the most consistent and strongest predictor of breast cancer risk. Now, newer studies show that this link depends on the menopausal stage of the woman. There is a strong relationship between obesity and increased breast cancer risk in postmenopausal women, but not in pre-menopausal women. Interestingly, research shows that among pre-menopausal women, a high BMI actually reduces the risk of breast cancer. However, postmenopausal women who gain a considerable amount of excess weight dramatically increase their risk of breast cancer. Cohort studies have shown that postmenopausal women whose BMI is in the top quartile increase their breast cancer risk by about 40 percent. Additionally, in the Women’s Health Study (1999–2004), women with a BMI greater than 40 kg/m² had a 60 percent higher risk of dying from cancers of all causes than women with a normal BMI. This increased risk is not impacted by lifestyle factors or physical activity. Researchers hypothesize that breast cancer risk after menopause may be mediated by the increase in endogenous estrogen production from excess adipose tissue.

Endometrial Cancer

A positive linear relationship exists between excess weight gain and risk for endometrial cancer, irrespective of menopausal status. Some studies suggest a linear increase risk of 200 to 400 percent for women with a BMI over 25 kg/m². Regardless of menopausal status, obese women are two to four times more likely to develop a uterine cancer than normal weight women.

Colon Cancer

Colon cancer also occurs more frequently in those who are obese compared to those who are of normal weight. Men with high BMI levels consistently show an increase risk of colon cancer; however, the evidence for women is not quite as strong. Weight gain in certain parts of the body may influence this risk. Specifically, abdominal fat seems to plays a role in the risk of colon cancer. Overweight men tend to collect fat in their abdomen, while in some women, fat is more likely to be distributed in the hips, thighs, and buttocks. Thus, it will be important for researchers to define the relationship between colon cancer and waist-to-hip ratio or waist circumference.

Meat and Protein

It is difficult to isolate effects of protein alone, since increased protein diets are often high in fat and low in fiber. However, it is clear that increased meat intake is associated with increased risk of colon cancer and advanced prostate cancer. Specifically, according to the AICR, there is significant evidence that red meat intake from beef, pork, lamb, and processed meats such as bacon, sausage, hot dogs, salami, ham, sandwich meat, and pepperoni significantly increase the risk of colorectal cancer. Researchers recommend eating a maximum of 18 ounces of cooked red meat per week and avoiding processed meat completely. In fact, for every additional ounce of processed meat consumed per day, the risk of colorectal cancer increases dramatically. Processed meats have also been linked to a higher incidence of stomach cancer.

Swedish researchers found a statistically significant increased incidence of stomach cancer in those who consumed high amounts of processed meat in a cohort study of over 60,000 women. They hypothesized that this increase risk may be due to the nitrates and nitrosamines found in these processed meats. Nitrites and nitrates react with amino acids to form cancer-causing nitrosamines. These compounds are used to provide a pink hue to cured meat without which the meat would turn brown during storage. Vegetables and fruit slow the conversion of nitrites to nitrosamines.

Other concerns with meat consumption involve cooking methods that use high temperatures such as frying, broiling, or barbequing. When meats such as beef, pork, poultry, and fish cook at high temperatures, the amino acids and creatine may form carcinogenic compounds called heterocyclic amines (HCAs). Researchers at the NCI have found 17 different HCAs formed from cooked meats that potentially cause cancer. A recent case-control study from the NCI found that people who regularly consumed beef medium-well or well-done increased their risk of stomach cancer by more than three times in comparison to those who consumed rare or medium-rare beef. Other NCI studies have shown that a high intake of well-done, fried, or barbecued meats is associated with an increased risk of developing colorectal, pancreatic, and breast cancer.

Carbohydrates, Fiber, and Whole Grains

The protective effects of eating whole grains to prevent cancer are not clearly established. However, many case-controlled studies have shown an association between high intakes of whole grains and low incidence of several types of cancer. A meta-analysis of 40 case-control studies that looked at 20 different types of cancer found that those with high whole grain intake had a 34 percent lower overall cancer risk than those with low whole grain intake. While a decreased risk of gastrointestinal tract cancers is most commonly associated with whole grain intake, the lignans in whole grains (phytoestrogens) may affect hormone dependent cancers as well.

Fiber is known to provide many health benefits such as reduced risk of heart disease and diabetes and prevention of constipation. Studies continue to confirm the link between eating fiber and a reduction in breast cancer risk. A recent study found that diets rich in dietary fiber and, particularly, fiber from vegetables was associated with reductions in breast cancer risk, independent of menopausal status.

Both soluble and insoluble fiber reduce the risk of breast cancer, especially for women consuming upwards of 30 g/day. Evidence from several studies suggests that women who consumed 30 g of fiber per day had a significant risk reduction (32 percent) of breast cancer. Compare that to the women who were eating less than 25 grams a day, who only had a very minimal risk reduction (2 percent). It is thought that insoluble fiber assists with the excretion of excess free estrogens in the gut. This ensures that less estrogen is free and absorbed, and consequently, the lower exposure to the hormone, the lower the risk of breast cancer.

Additionally, The European Prospective Investigation into Cancer and Nutrition (EPIC) project first demonstrated years ago that a high fiber diet was associated with a decreased risk of colon cancer. In 2012, they did a retrospective cohort study and found that total dietary fiber was inversely associated with colorectal cancer.

Fats

While total fat intake does not seem to alter cancer risk, diets high in animal fats are positively associated with colorectal and prostate cancer. Recently, omega-3 fatty acids from fish oils have received a lot of attention for their heart health and anti-inflammatory benefits. Omega-3 fatty acids, DHA and EPA, are converted into anti-inflammatory prostaglandins, which researchers believe may reduce tumor growth. Omega-3 fatty acids may be beneficial, omega-6 fatty acids may actually be harmful and promote prostate cancer. Omega-6 fatty acids cause the production of a family of eicosanoids including prostaglandins, which affect immunity and promote inflammation. The health impact of these various fatty acids is related to the ratio of omega-6: omega-3 fatty acids consumed. In the United States, 60 years ago, people consumed a dietary ratio of omega-6 to omega-3 that was about 2 : 1. Today, the ratio is roughly 25 : 1. Over these 60 years, the incidence of prostate cancer in the United States has grown steadily. Scientists have demonstrated in cell culture that omega-6 fatty acids cause increased production of cytosolic phospholipase A2 (cPLA2), which causes the production of the enzyme Cyclooxygenase-2 (COX2). COX2 stimulates the release of prostaglandin E2 (PGE2) and promotes cell growth, a process that may ultimately lead to cancer.

Phytochemicals

Phytochemicals are compounds found in plants that have the ability to protect the plant against disease and bacterial or fugal infections. Research shows that these compounds may play an important role in preventing tumor growth in humans. Over 4000 different types of plant phytochemicals have been identified. Two main classes of phytochemicals include, carotenoids and flavonoids, as shown in Table 11-1, but there are several other families of phytochemicals including other polyphenols, sulfur compounds, and saponins.

Flavonoids are found in grapes, apples, berries, green tea, and red wine, along with many other foods. The chemical structure of these polyphenols makes them ideal for absorbing free radicals, and as effective antioxidants. Free radicals are unstable molecules produced by the cell that ultimately lead to cell damage and may cause cancer. Antioxidants interact with and stabilize free radicals and thus prevent them from causing harm to cells.

Berries

Blackberries, raspberries, strawberries, blueberries, cranberries, lingonberries, and deerberries (either winter green berry or partridge berry) all have a high content of flavonoids that absorb free radicals. Berries contain a unique phytochemical compound known as ellagic acid that may have the capacity to interfere with tumor genesis. Ellagic acid is a polyphenol antioxidant found in high concentrations in raspberries, pomegranates, and strawberries. In a recent study from the Hollings Cancer Institute, researchers demonstrated that ellagic acid can stop cancer cells from dividing for 48 hours. Ellagic acid can also cause apoptosis (cell death) within 72 hours in cultures of breast, pancreas, esophageal, skin, colon, and prostate cancer cell lines. Additionally, ellagic acid prevents the oxidation of the p53 gene that may lead to cancer. It is important to note that most studies investigating the properties of ellagic acid have been conducted in cell cultures and laboratory animals. While human research with ellagic remains preliminary, there are several theories about the mechanism of action of this phytochemical. Ellagic acid may work by preventing the activation of carcinogenic substances in the body. Ellagic acid may also be a powerful inhibitor of tumor angiogenesis.

Raspberries and blueberries contain another class of polyphenol compounds called anthocyanidins, which are responsible for the blue and red colors of berries. Anthocyanidins are among the most potent antioxidants ever discovered. In isolated laboratory cancer cells, anthocyanidins stopped cells from synthesizing DNA and caused apoptosis. Anthocyanidins may also inhibit tumor angiogenesis. Other laboratory studies have shown that these phytochemicals inhibit the growth of lung, colon, and leukemia cancer cells while sparing healthy cells. This evidence puts berries at the top of the list of potential cancer-fighting foods (Table 11-2).

Fruits and Vegetables

Vegetables Both the ACS and AICR recommend maintaining a diet rich in fruits and vegeta­bles to reduce the risk of cancer. In particular, several cohort case studies suggest that fruits and vegetables may protect against cancers of the oropharynx, esophagus, stomach, colon, rectum, and lung. However, overall, the results of studies linking cancer prevention to fruit and vegetable consumption have been inconclusive and inconsistent. Specifically, prospective cohort studies show a weak link between cancer risk reduction and fruit and vegetable intake. Despite weak data from prospective cohort studies concerning overall vegetable intake, there is significant evidence that high intakes of specific types of vegetables, such as cruciferous vegetables may reduce cancer risk. Cruciferous vegetables include cabbage, broccoli, Brussels sprouts, cauliflower, collard greens, kale, mustard, rutabaga, turnips, bok choy, Chinese cabbage, arugula, radishes, and several others. Such vegetables contain high concentrations of a group of sulfur compounds called glucosinolates. The breakdown of glucosinolates results in the release of indoles and isothiocyanates. This hydrolysis may be accomplished when these vegetables are chopped or chewed and come in contact with a plant enzyme called myrosinase. Indoles and isothiocynates may help prevent cancer by eliminating carcinogens, altering cell signaling pathways, or changing the metabolism and activity of certain hormones. For example, one study showed that consumption of 250 g/day of broccoli and 250 g/day of Brussels sprouts caused an increase in the urinary excretion of a possible carcinogen found in well-done meat. This suggests that such high intakes of cruciferous vegetable may decrease cancer risk by helping to eliminate certain carcinogens found in food. Some studies have shown that cruciferous vegetables may also help prevent breast and prostate cancer, but currently the data remain inconsistent and indefinite.

Two other molecules have received attention for their potential cancer fighting properties: sulforaphane and indole-3-carbinol (I3C). Studies show that sulforaphane, an isothiocynate found in high concentrations in broccoli, has the ability to both cause excretion of toxic, cancer-causing substances from the body and cause cell death in tumor cells. Indole-3-carbinol is produced by the hydrolysis of glucosinolates but contains no sulfur atoms. Recent research has focused on I3C’s ability to influence estrogen metabolism. I3C may play an important role in cancers that are dependent on estrogen such as breast, cervical, and uterine cancers. Several factors must be considered to maximize the indole and isothiocyanate content in these vegetables. Glucosinolates are extremely water-soluble and boiling cruciferous vegetables in water for more than 10 minutes may reduce the amount of glucosinolates by half. Steaming or stir-frying is a more effective way to maximize the amount of cancer-fighting compounds present in these vegetables. While NCI recommends consuming 5 to 9 servings of fruits and vegetables, there is currently no specific recommendation on cruciferous vegetable consumption.

Tomatoes Tomatoes have a high concentration of the carotenoid lycopene. Carotenoids are the molecules in fruits and vegetables that are responsible for their vibrant colors such as red, oranges, and yellows. Some carotenoids, such as beta-carotene, are precursors to vitamin A. Lycopene is not related to vitamin A, but it may be the carotenoid with the greatest cancer fighting potential. The association between lycopene and prostate cancer came from observations that countries where there is high tomato consumption such as Italy, Spain, and Mexico have much lower rates of prostate cancer compared to the United States or England. Several studies have shown that individuals who consume large amounts of tomatoes and tomato products have a reduced risk of developing prostate cancer. However, different tomato products contain variable concentrations of lycopene. For example, while tomato paste may contain 29.3 mg per 100 grams, canned tomatoes may contain only 9.7 mg per 100 grams. This variability makes it difficult to come to any definitive conclusions linking tomato products and prostate cancer prevention, but absorption is enhanced when eaten with fat.

Not all carotenoids demonstrate promising anticancer effects. Beta-carotene is a carotenoid found in many foods that are orange in color, including sweet potatoes, carrots, cantaloupe, squash, apricots, pumpkin, and mangos. In 1994, a cancer prevention study known as the Alpha-Tocopherol (Vitamin E)/Beta-Carotene Cancer Prevention Study (ATBC) found that lung cancer rates of male smokers actually increased with beta-carotene supplementation. A meta-analysis of randomized controlled trials, published in 2009, looked at the effect of beta-carotene supplementation on cancer incidence and showed that, specifically, the incidence of lung and stomach cancers were significantly increased in individuals who used beta-carotene supplements at 20 to 30 mg/day, in smokers and asbestos workers compared to the placebo group.

Overall, beta-carotene supplementation has not been shown to have any beneficial effect on cancer prevention and such supplements should not be recommended. Smokers should now be warned not to take beta-carotene supplements. Thus, current research suggests that any benefit from foods containing phytonutrients cannot automatically be related to their individual constituents.

Garlic Garlic is part of a larger group of vegetables known as the Allium family, which includes onions, scallions, leeks, and chives. Allium vegetables possess a sulfur-containing compound called alliin that is converted to allicin when raw garlic is crushed, chewed, or chopped by an enzyme known as allinase. Allicin then quickly converts to a number of other compounds including diallyl sulfide (DAS), diallyl disulfide (DADS), and ajoene.

In the lab, DAS and DADS have shown promising effects on cancer prevention and progression through two main mechanisms: the ability to prevent the activation of carcinogenic substances and the potential to induce apoptosis in tumor cells. In laboratory studies, DAS inhibits cancer progression and onset in animals in which cancer was induced by carcinogenic substances. Garlic seems especially protective against cancers caused by nitrosamines, which are chemical compounds commonly found in preserved meat products such as salami, bacon, and sausage. In addition to garlic’s action on carcinogenic substances, researchers believe that garlic may have the ability to directly attack and destroy tumor cells. Cancer is characterized by unregulated cell division, and organosulfur compounds such as DADS and ajoene have the ability to induce cell cycle arrest when added to cancer cells in cell culture. Additionally, DAS has the greatest ability to induce apoptosis in cancer cells grown in culture. According to AICR, DAS has actually killed leukemia cells in the laboratory, and ajoene has shown some similar effects. While more studies are needed before dietary recommendations can be made, garlic continues to hold a place in the list of foods that fight cancer.

Soy and Breast Cancer

Soybeans are legumes used to make tofu, soy milk, miso, tempeh, soy burgers, soy sauce, and soynut butter. Soy contains a class of phytochemicals called isoflavones. The main isoflavones in soybeans are genistein and daidzein. These compounds are similar in structure to human estrogen. Thus, isoflavones are often referred to as phytoestrogens. There is growing evidence for a beneficial action of isoflavones on various cancer-related biological pathways, such as cell-signaling, carcinogen activation, cell cycle regulation, angiogenesis, oxidative stress, and chronic inflammation. Researchers originally associated soy with reduced breast cancer risk after observations of diet differences in Eastern and Western cultural diets. The low rate of endometrial and breast cancer in Asia may be due to women’s dietary habits and their high consumption of soy. Based on these initial observations, several studies have examined the influence of soy on breast cancer risk. The prevailing hypothesis is that phytoestrogens compete with estradiol for the binding sites on intracellular estrogen receptors. These phytoestrogens are acting as selective estrogen receptor modulators (SERMs). For example, genistein binds to estrogen receptors with a weaker affinity, which does not produce as strong of a cellular response but blocks estrogen from reaching the receptors – therefore potentially protecting women from developing breast cancer. Several studies have shown that consumption of soy (55 g/day or more) reduces women’s risk of developing breast cancer. Studies have found that pre-menopausal women may benefit from eating soy foods since their natural estrogen levels are high. However, another large study showed no correlation between soy intake and the risk of developing breast cancer. These contrasting effects may be due to the amount of isoflavone consumed in the studies or the timing of soy consumption (e.g., ingestion during adolescence). There may be a certain threshold needed for soy consumption before the protective effects are realized.

Another key factor that may influence the effect of soy on breast cancer risk is the age at which soy is introduced into the diet. Most studies have shown strong evidence for a decrease in breast cancer occurrence in women who consumed soy before puberty and during adolescence. AICR and the American Cancer Society (ACS) stress that data on soy and breast cancer are not conclusive. Additionally, many studies showing the positive impact of soy on breast cancer have been done exclusively in Asian women. Possible genetic differences in phytoestrogen metabolism make it difficult to extrapolate these results to non-Asian women. More information is needed before any dietary recommendations can be made. One exception to this rule may be for women who have estrogen-receptor positive breast cancer or those taking anti-estrogen medications such as tamoxifen or aromatase inhibitors. According to AICR, patients taking such medication should limit or avoid soy intake until further studies are conducted.

Soy and Prostate Cancer

The role of soy phytoestrogens in prostate cancer is also controversial. While treating prostate cancer with estrogens inhibits cancer growth, estrogens have also been associated with the growth of both benign prostatic hyperplasia and prostate cancer. In a small study, Australian researchers found that men consuming a soy-enriched diet had a statistically significant drop of 12.7 percent in prostate-specific antigen (PSA) levels, compared to the control group whose PSA levels rose 40 percent. Additionally, researchers showed that by adding about 2 ounces of soy grits a day to the diets of men diagnosed with prostate cancer, they could cause quick and noticeable improvements in the subjects’ PSA levels. PSA is commonly used to screen for prostate cancer and for tracking the disease once it has been diagnosed. Soy grits are soybeans that have been toasted and cracked into coarse pieces. During the late 1980s, researchers found that Japanese men in Hawaii who ate tofu at least 5 times per week had 65 percent less chance of developing prostate cancer than those who ate tofu only once a week or less. In 1998, a study involving 12,395 men showed that men who drank a serving of soy milk at least once a day had a 70 percent less chance of developing prostate cancer than those who never drank soy milk. Soy has also been found to be potentially beneficial in treating prostate cancer and slowing its progression in many animal and in vitro studies. Lately, more human studies point to similar results. Despite these optimistic results, another study that followed 5855 Japanese American men for over 20 years found no association between tofu intake and prostate cancer risk. It is important to note the limitations of any cohort case study in which the data is based on dietary questionnaires and recall.

It has been speculated that the incidence of prostate cancer in Eastern Asia is lower than in Western societies because of high soy consumption in Asia. In a meta-analysis including five cohort and nine case-control studies, total consumption of soy foods and non-fermented soy foods were inversely associated with prostate cancer risk. However, in that meta-analysis, the inverse association between soy food consumption and prostate cancer risk was only seen in Asian men, whereas no association was seen among studies on men from Western societies. There are many possible explanations for this observation. For example, it could be that different types of soy foods are consumed in Asian and Western countries, or that the amount soy food consumed in Western countries has failed to reach the threshold needed to produce an inverse association with prostate cancer.

Several mechanisms have been proposed for how isoflavones may impact prostate cancer. These include blocking androgen receptors, inhibiting tyrosine protein kinases and growth factor receptors, and preventing tumor angiogenesis. Still, researchers are not clear whether the benefits of soy seem to have on men’s health are due to the soy protein, the isoflavones, daidzein, and genistein, or a combination. What is clear is that there are far more prostate cancers in the West compared to the East, and this may be attributable, in part, to the differences in diet and lifestyle.