**5. Minerals and trace elements**

**Nutrient Active component Known function** Tea phytochamicals Antioxidant Chocolate Polyphenols Antioxidant

184 Pharmacology and Nutritional Intervention in the Treatment of Disease

Plants Phytochemicals Hydroxyl scavenger

Soybean Isoflavones estrogen-like action Garlic and Onions Flavanoids, sulfur disposal of carcinogens Vegetables flavanoids, Indoles DNA damage protection

Vitamin E Vitamin E Lipid peroxidation protection

As can be seen from table 3, a large number of constituents in fruits, vegetables, green tea, grapes, pepper, red wine and salmon possess substances that have anticancer potential. Apart from the carcinogen exposure from the immediate environment, a number of substances in cooked, grilled and smoked meat can contribute to the carcinogenic load of the cells in the body. The extents to which such carcinogens induce cancer development depend on the quality and quantity of the food consumed regularly and the concentration of scavengers available during the metabolism of cells. During the intermediate stage of cancer development, the restricted energy intake and increased physical activity can have significant additive effect on

Reactive oxygen species are also known to be associated with aging process in a number of species, including humans. It is a common observation that the prevalence of many human cancers is high in aging populations. Average life-span in most developed coun‐ tries as well as in many fast-growing developing countries in Asia, Africa and Latin America has increased tremendously during the last few decades. According to several research groups, cellular damage caused by oxidation is one of the main mechanisms of aging. According to this theory, rampant oxidation in the cells mangles more and more lipids, proteins, and snippets of DNA and other key components of cells over time, eventually compromising tissues and organs and thus resulting in organ failure. Recent studies, however, showed that increase in certain free radicals in mice and worms correlate larger life span. Indeed, in some circumstances, reactive oxygen species seem to signal cellular repair methods. Experimental studies by several groups in the United States of America

Grapes Catechin Antioxidant Olives Polyphenols Antioxidant

Selenium Antioxidant enzymes Antioxidant Vitamin C Vitamin C Scavenger of ROS

Beta-Carotene provitamin A Antioxidant Tomatoes, salmon Lycopene Antioxidant Red wine Phenols Antioxidant

cancer development through the action of hormones and growth factors.

**Table 3.** List of selected nutrients that have antioxidant potential

Many of the minerals and trace elements are nutrients that cannot be synthesized by the body. They are involved in all phases of cellular metabolism in one way or another. Trace elements are integral parts of very many enzymes including the ones that scavenge ROS.The minerals and trace elements that are of interest include calcium (together with vitamin D), magnesium, iodine, iron, selenium and zinc. Evidence suggesting the relationship of other minerals and toxic heavy metals with cancer is not substantial and as such, they are not described in this review. The dietary intake of minerals and trace elements in various parts of the world vary significantly due to varied eating habits, culture and tradition, climatic conditions and the amount present in the soil. Studies by the current authors indicate that the intake of a number of important trace elements and minerals is below the current recommended levels [18].The intake levels are especially low in the elderly [18].The richest source of calcium is dairy products and fish. Selenium levels in the soil vary greatly in different regions of the world. Australia, New Zealand and Scandinavian countries have low selenium levels in the soil. Selenium is mainly found in meat, fish and certain cereals [18].Hem iron is mainly found in foods of animal origin. Non-hem iron is found in plant foods and legumes. Zinc is rich in seafood, meat and unprocessed vegetable material. Oysters are one of the richest sources of zinc. Modern food processing destroys significant amounts of trace elements than found in the natural material. For iodine, the best sources are sea food and seaweed.

Evidence on the relationship between calcium and cancer was considered by the 1982 and 1989 reports of the national Academy of Science [19, 20]. According to the report, there are some epidemiological evidence linking high calcium intake and the cancers of colon and rectum. High calcium intake together with vitamin D has also been documented to have some effect in the risk of developing colorectal cancer. Data for other cancer sites linking calcium intake is inconclusive.

research since Cristo in 1922 showed high amounts in cancer tissues [22].Many research groups in the past have shown that patients with cancer in general have low plasma zinc levels. It is assumed that this decrease is due to the high demand of the tumor tissue, especially when they have a high rate of DNA synthesis. As mentioned earlier, zinc is essential for growth and development of normal tissues and as such it may be needed even more in cancer tissues. Opinion, however, differs regarding the role of zinc in the induction and proliferation of malignant cells. A high zinc intake has been associated with lower incidence of gastric and esophageal cancers in certain parts of the world. Our own studies have shown that low dietary zinc inhibit the growth of oral cancer in experimental animals [22]. Once the tumor starts growing, the requirement becomes high and plasma levels go down. Many essential trace elements like zinc have dual functions: in low concentrations, they show signs of specific disease and at high concentrations, signs of toxicity. Iron is a trace element that shows such a pattern: when the intake is low, it produces anemia and at higher concentrations, it shows toxicity symptoms such as hemochromatosis and liver injury. In general, only little is known

Dietary Aspects in Cancer Prevention — A Mini-Review

http://dx.doi.org/10.5772/57371

187

Cancer is a major killer throughout human history. In 2008, there were an estimated 12.7 million cancer cases throughout the world. This number is expected to increase to 21 million by 2030. Cancer changed its grasp as humans advanced industrially and technologically. Although the risk of a few cancers has declined significantly in affluent countries during the last few decades, the incidence of other cancers at sites of lung, breast and prostate has increased. Lung cancer is the most common cancer worldwide contributing nearly 13% of the cases diagnosed in 2008.Breast cancer (in women) is the second followed by colorectal cancer. Carcinogenesis encompasses a prolonged accumulation of injuries at several different biological levels and includes both genetic, biochemical and environmental changes in the cells. At each of these levels, there are several possibilities of intervention in order to prevent, slow down or even halt the gradual march of healthy cells to malignancy. Diet modification is one such possibility. A number of natural foodstuffs, especially fruits and vegetables contain significant quantities of molecules that have chemoprotective potential against cancer devel‐ opment. Such molecules include vitamins, certain mineral and trace elements and a variety of other substances with antioxidant properties. Carotenoids, flavanoid polyphenols, osofla‐ vones, catechins, and several other compounds found in cruciferous vegetables are molecules that are thought to protect against the deleterious effect of reactive oxygen species (ROS).A number of epidemiological and experimental studies have shown that some of the abovementioned antioxidants can reduce the risk of cancer. Consistent observations during the last few decades that cancer risk can be reduced by diets rich in fruits and vegetables, legumes, grains, nuts, green tea and red wine have encouraged research to identify several plant components, especially phytochemicals that protect against DNA damage. Many of these substances are known to block specific carcinogen pathways. Very recent studies have, however, questioned the role of ROS, aging and cancer development. Certain reactive oxygen

about the role of trace elements in carcinogenesis.

**6. Summary**

With regards to iron and cancer, there is some evidence that diets high in iron may possibly increase the risk of liver and colorectal cancers in humans. In humans, the dietary iron overload is rare except in some ethnic groups in Africa where iron utensils are widely used for cooking. Data from case-control studies are, however, inconsistent. Iodine in the body is related to thyroid function and it has been proposed that a high intake of iodine may induce thyroid cancer. Ecological and experimental studies support the association between high dietary intake and the risk of developing thyroid cancer.

Selenium has attracted consider interest in cancer research during the middle part of twentieth century. During the early 1960´s, it was shown that selenium is an integral part of the antiox‐ idant enzyme, glutathione peroxidase [19]. Currently, selenium is also recognized as an essential component of iodothyronine 5´-deiodinases as well as a few other proteins without any known functions. During the last few decades, a number of experimental studies have indicated the importance of this trace element for cancer prevention. A few epidemiological studies have confirmed such an association even in humans. Several selenium compounds have been found to inhibit or retard carcinogenesis in a variety of experimental animal models using chemical, viral and transplanted tumor models. A prospective case control study in Finland showed a link between selenium status and cancer development. Studies of humans have tended to show selenium status and cancer mortality to be inversely correlated. The soil in Finland was enriched by selenium due to low levels in the environment and studies afterwards did not show any specific pattern on the relationship between selenium and cancer. Other epidemiological studies in low soil areas have failed to show the protective effect of selenium on cancer development. Any potential anticarcinogenic influence of this trace element may relate to its antioxidant properties. This, however, is controversial at present. In some studies, selenium has been shown to suppress cell proliferation, to enhance immune response, and to alter the metabolism of carcinogens to less toxic compounds [21]. The overall interest in selenium as a protective trace element against cancer, however, has faded during the last two decades.

Zinc is another trace element that has attracted considerable interest in human health and disease. Zinc was recognized as an essential nutrient for human growth and development several decades ago. Marginal deficiency of zinc is widespread throughout the world. The prevalence of nutritional zinc deficiency is high in populations consuming large amounts of cereal proteins which contain organic phosphate compounds, such as phytate.Even in affluent countries; it has been observed that mild deficiency of zinc occur in vulnerable groups such as the elderly [18]. Hormonal effects of zinc deficiency include decreased testosterone level in serum of males, increased serum prolactin levels, and decreased activity of serum thymulin, a zinc-dependent thymic hormone. This trace element has attracted much interest in cancer research since Cristo in 1922 showed high amounts in cancer tissues [22].Many research groups in the past have shown that patients with cancer in general have low plasma zinc levels. It is assumed that this decrease is due to the high demand of the tumor tissue, especially when they have a high rate of DNA synthesis. As mentioned earlier, zinc is essential for growth and development of normal tissues and as such it may be needed even more in cancer tissues. Opinion, however, differs regarding the role of zinc in the induction and proliferation of malignant cells. A high zinc intake has been associated with lower incidence of gastric and esophageal cancers in certain parts of the world. Our own studies have shown that low dietary zinc inhibit the growth of oral cancer in experimental animals [22]. Once the tumor starts growing, the requirement becomes high and plasma levels go down. Many essential trace elements like zinc have dual functions: in low concentrations, they show signs of specific disease and at high concentrations, signs of toxicity. Iron is a trace element that shows such a pattern: when the intake is low, it produces anemia and at higher concentrations, it shows toxicity symptoms such as hemochromatosis and liver injury. In general, only little is known about the role of trace elements in carcinogenesis.

### **6. Summary**

Evidence on the relationship between calcium and cancer was considered by the 1982 and 1989 reports of the national Academy of Science [19, 20]. According to the report, there are some epidemiological evidence linking high calcium intake and the cancers of colon and rectum. High calcium intake together with vitamin D has also been documented to have some effect in the risk of developing colorectal cancer. Data for other cancer sites linking calcium intake

With regards to iron and cancer, there is some evidence that diets high in iron may possibly increase the risk of liver and colorectal cancers in humans. In humans, the dietary iron overload is rare except in some ethnic groups in Africa where iron utensils are widely used for cooking. Data from case-control studies are, however, inconsistent. Iodine in the body is related to thyroid function and it has been proposed that a high intake of iodine may induce thyroid cancer. Ecological and experimental studies support the association between high dietary

Selenium has attracted consider interest in cancer research during the middle part of twentieth century. During the early 1960´s, it was shown that selenium is an integral part of the antiox‐ idant enzyme, glutathione peroxidase [19]. Currently, selenium is also recognized as an essential component of iodothyronine 5´-deiodinases as well as a few other proteins without any known functions. During the last few decades, a number of experimental studies have indicated the importance of this trace element for cancer prevention. A few epidemiological studies have confirmed such an association even in humans. Several selenium compounds have been found to inhibit or retard carcinogenesis in a variety of experimental animal models using chemical, viral and transplanted tumor models. A prospective case control study in Finland showed a link between selenium status and cancer development. Studies of humans have tended to show selenium status and cancer mortality to be inversely correlated. The soil in Finland was enriched by selenium due to low levels in the environment and studies afterwards did not show any specific pattern on the relationship between selenium and cancer. Other epidemiological studies in low soil areas have failed to show the protective effect of selenium on cancer development. Any potential anticarcinogenic influence of this trace element may relate to its antioxidant properties. This, however, is controversial at present. In some studies, selenium has been shown to suppress cell proliferation, to enhance immune response, and to alter the metabolism of carcinogens to less toxic compounds [21]. The overall interest in selenium as a protective trace element against cancer, however, has faded during

Zinc is another trace element that has attracted considerable interest in human health and disease. Zinc was recognized as an essential nutrient for human growth and development several decades ago. Marginal deficiency of zinc is widespread throughout the world. The prevalence of nutritional zinc deficiency is high in populations consuming large amounts of cereal proteins which contain organic phosphate compounds, such as phytate.Even in affluent countries; it has been observed that mild deficiency of zinc occur in vulnerable groups such as the elderly [18]. Hormonal effects of zinc deficiency include decreased testosterone level in serum of males, increased serum prolactin levels, and decreased activity of serum thymulin, a zinc-dependent thymic hormone. This trace element has attracted much interest in cancer

is inconclusive.

the last two decades.

intake and the risk of developing thyroid cancer.

186 Pharmacology and Nutritional Intervention in the Treatment of Disease

Cancer is a major killer throughout human history. In 2008, there were an estimated 12.7 million cancer cases throughout the world. This number is expected to increase to 21 million by 2030. Cancer changed its grasp as humans advanced industrially and technologically. Although the risk of a few cancers has declined significantly in affluent countries during the last few decades, the incidence of other cancers at sites of lung, breast and prostate has increased. Lung cancer is the most common cancer worldwide contributing nearly 13% of the cases diagnosed in 2008.Breast cancer (in women) is the second followed by colorectal cancer. Carcinogenesis encompasses a prolonged accumulation of injuries at several different biological levels and includes both genetic, biochemical and environmental changes in the cells. At each of these levels, there are several possibilities of intervention in order to prevent, slow down or even halt the gradual march of healthy cells to malignancy. Diet modification is one such possibility. A number of natural foodstuffs, especially fruits and vegetables contain significant quantities of molecules that have chemoprotective potential against cancer devel‐ opment. Such molecules include vitamins, certain mineral and trace elements and a variety of other substances with antioxidant properties. Carotenoids, flavanoid polyphenols, osofla‐ vones, catechins, and several other compounds found in cruciferous vegetables are molecules that are thought to protect against the deleterious effect of reactive oxygen species (ROS).A number of epidemiological and experimental studies have shown that some of the abovementioned antioxidants can reduce the risk of cancer. Consistent observations during the last few decades that cancer risk can be reduced by diets rich in fruits and vegetables, legumes, grains, nuts, green tea and red wine have encouraged research to identify several plant components, especially phytochemicals that protect against DNA damage. Many of these substances are known to block specific carcinogen pathways. Very recent studies have, however, questioned the role of ROS, aging and cancer development. Certain reactive oxygen species have been found to be useful as part of the defense mechanism. Other studies have shown that high doses of anti-oxidant supplements may not provide protection against ROS as it was originally thought. We need a lot more proof about the role of ROS in health and disease. The debate on the role of antioxidants as protective agents against cancer is likely to continue. Only little is known about the role of trace elements in cancer.

[16] B.Carmia. Env Hlth Pers 1993;101(3) 237-245.

[19] NAS. National Academy Press, Washington DC, 1989.

[23] M.Abdulla and P.Gruber. BioFactors 2000;12 45-51.

[20] Am inst cancer res. World cancer research fund, Washington DC, 1997. [21] G.F.Combs. In "Antioxidants and disease Prevention, CRC Press, 1997.

[18] M.Abdulla. Thesis, Inorganic chemical elements in prepared meals, University of

Dietary Aspects in Cancer Prevention — A Mini-Review

http://dx.doi.org/10.5772/57371

189

[22] A.Mathur and M.Abdulla. Role of zinc in oral cancer, University of Lund, Sweden,

[24] P.Boyle and B.Levin IARC. Nonserial publication, World cancer report, 2008. [25] M.W.Moyer. The myth of Antioxidants. Scientific American 2013, 308(2) 56-61.

[17] B.Carmia. Science and Medicine 1997; 52

Lund, 1985.

1978.
