Colorectal Cancer Incidences and Dietary Lifestyle in Developed and Less Developed Countries:  An Empirical Study

Kavya Vaidyanathan[1]

University of Michigan, Ann Arbor, Michigan

Abstract

Colorectal cancer is a common cancer in many western countries. Research suggests that a diet that is high in meats, refined grains, and sugar and that is low in vegetables and fiber may increase the risk of colorectal cancer. Results of epidemiological studies indicate that a diet rich in vegetables may lower the incidence of colorectal cancer. This research study focuses on the cancer deaths and occurrences in various countries.  In particular, this study compares the colorectal cancer deaths and occurrences in developed countries to less developed nations. The study is designed using existing international databases to understand the effect of vegetable/fruit consumption over meat consumption on colorectal cancer rates. Data were analyzed to calculate the correlations between colorectal cancer and vegetable/fruit consumption over meat consumption. The results indicated that diet with high meat to vegetable/fruit consumption in developed countries plays a significant role in the higher amount of colorectal cancer over the developing counties.  Using data for over 50 countries, the results also indicate that there is a significant association between higher vegetable and fruit consumption over meat consumption on colorectal cancer rate. 

Introduction

Cancer is the second leading cause of deaths in the Unites States. The cancer of the colon or the rectum, together known as colorectal cancer, is the third most frequently occurring cancer among both men and women and is the cancer that has the second highest rate of killing infected patients (Preventcancer.org, 2003).  The American Cancer Society estimates that there will be about 105,500 new cases of colon cancer and 42,000 new cases of rectal cancer in 2003 in the United States. Combined, they will cause about 57,100 deaths.

Considerable amount of research indicate significant effects of nutrients on cancer rates. This study is aimed at vegetable/fruit consumption over meat consumption in more than fifty countries and its effect on colorectal cancer incidence rates. 

Colorectal Cancer

The colon and the rectum together form the large intestine, where the colon is the first six feet of the large intestine and the rectum is the last 8-10 inches (U.S. National Cancer Institute, 2003). Indigestible waste fluids and certain minerals enter the large intestine, where much of the water and the minerals are reabsorbed. The remaining solid feces that contain millions of bacteria finish passing through the intestine before exiting through the anal canal (Winawer, 1995).

Colorectal cancer begins from a small polyp. Polyps, or small bumps along the lining of the intestine, form when there is a build-up of cells. Polyps are common especially in men and women who are at least 50 years of age. Although one third of polyps are harmless, the other two-thirds are adenomas, which have a five percent chance of progressing into cancer.  It normally takes a polyp 5-10 years to transform into cancer in adults (Winawer, 1995).

A regular examination of the large intestine for polyps is a sure way to prevent this cancer. Symptoms include cramps, gas pains, bloating, and changes in bowel habits such as constipation and diarrhea, chronic tiredness, and dark or bright red blood in the stool (Winawer, 1995).

Nutrition, diet and diseases

For a very long time, scientists have analyzed foods.  To begin with, scientists introduced factors for calculating caloric value for foods. They measured the amount of food that people ate and calculated what these amounted to in protein, carbohydrate, and energy.  Atwater and Benedict (1899) showed that the available energy produced by food eaten by an individual equaled the energy lost by the individual in heat.  They compiled the chemical composition of American food materials (Atwater, 1906).

Long after Hopkins discovered vitamins, scientists realized that vitamins helped human body to grow and maintain health.  Then research was directed to analyze how nutrients help reduce risks associated with certain diseases.  Rickets was most likely the first disease that pointed directly to a deficiency of vitamins in the body, and cod liver oil was used to cure the disease as early as the 18^th century.  Szent-Gyorgyi (1928) showed that a certain substance extracted from ox suprarenal glands protected guinea pigs against scurvy.  Later on, King and Waugh (1932) identified that substance as Vitamin C.

Osborne and Mendel (1913) showed that green vegetables, known to contain yellow pigments carotene and xanthophylls, were effective as a source of fat-soluble A, and Steenbock (1919) later demonstrated that the carotene was the active pigment.  Chick, et al. (1923) discovered that provitamin 7 dehydrocholestrol and ultraviolet rays formed Vitamin D3 and D2 in the skin to cure rickets along with cod liver oil.  Vitamin B was found to cure beriberi by Smith and Hendrick (1926).  Rickes et al. (1948) isolated vitamin B12 and showed that B12 was active in the treatment of pernicious anemia (West, 1948).

Deficiencies of nine of the trace elements that include iodine, iron, zinc, copper, chromium, selenium, molybdenum, manganese, and cobalt, have been reorganized in humans (Sandstead, 1984) in addition to cadmium and methyl mercury.  In the same study, it has been pointed out that nickel, arsenic, and boron are now known to be required. 

The observation that iodine cured goiter and the suggestion that goiter might be caused by a deficiency of iodine was made by French physicians in the early 1890s.  The necessity of Zinc for proper nuclear acid and protein synthesis, cell division and hypertrophy, tissue growth, maturation, cellular and humoral immunity, and metabolism of carbon dioxide and superoxide, had been discovered by then (Prasad, 1982 and Valle, 1983).  Zinc deficiency is common among poor populations that subsist on cereals and other foods of vegetable origin and those who do not eat red meat, organ meats, and certain crustaceans and shellfish (Sandstead, 1982).

Iron deficiency is the most widespread nutrition deficiency in the world.  Research has focused on a diagnosis as well as on the effects of anemia, iron metabolism, and iron bioavailability (Edgerton, 1982). The central nervous system is influenced by iron nutrition (Pollitt, 1982).  Copper has been recognized as being important to cardiovascular health. Experimental copper deficiency has been shown to debilitate glucose utilization (Klevay, 1982) and elevate serum cholesterol (Klevay, 1980).

Chromium supplements corrected impaired glucose and amino acid utilization, poor responsiveness to exogenous insulin, weakness, and weight loss in a patient (Schroeder, 1970).  Discovery in China showed that in a certain province children exhibited cardiomyopathy and death because of selenium deficiency (Ge, 1982).  These findings from China demonstrate that humans who consume foods from a limited geographic area have a potential risk of deficiencies of essential elements similar to farm animals (Sandstead, 1984).

Environmental toxins such as lead, cadmium, and methyl mercury need to be monitored carefully as pointed out by research (Mahaffee, 1982).  Some epidemiological studies seemed to find a decreased risk of colon cancer associated with eating certain cruciferous vegetables (Armijo, 1981).  Selenium and Fiber have been long researched in this topic. 

It is difficult to pinpoint a direct influence of a specific genotoxin in the customary food supply in Western Countries.  Their concentrations are generally low and are usually monitored in United States. Substances found in food such as N-nitroso compounds, hydrazines, safrole, cycasin or pyrrolizidine alkaloaids have been found to be carcinogenic in animals. Some of these compounds occur in U.S. diet in very small amounts (Wynder, 1984).

N-nitroso compounds (nitrosamines) are an important class of environmental carcinogens that have caused tumors in experimental animals.  Exposure to nitrates, nitrites, and N-nitroso compounds comes from various sources.  Nitrate and Nitrite may occur as a result of food processing (Wynder, 1984).  Some vegetables and fruits naturally contain large amounts of nitrate; however, they have ascorbic acid, which is an inhibitor of nitrosation.  Nitrate and nitrite in soil and drinking water may be associated with an increased incidence of stomach and esophageal cancer (Cuello, 1976).  Because chemicals that cause mutations have a higher probability of being initiators of carcinogenesis, mutagens need to isolated and tested for carcigogenicity in animals.

In a study, observations were made that milk and several vegetables have been consumed with less frequency by colorectal cancer cases than by controls (Bjelke, 1978). 

Dietary lifestyle and colorectal cancer

Of the cancers that are known to us, we focus on colorectal cancer in this study.  The lifetime probability of developing colorectal cancer is 1 in 17 for men and 1 in 18 for women (Curry, 2003).  A personal history of colorectal polyps, or chronicinflammatory bowel disease, or a family history of hereditary colorectal cancer syndrome places individuals at higher risk for these types of cancer (American Cancer Society, 2002).

The ways in which diet might affect cancer are as follows:

1. Ingestion of carcinogens:
   a. In Natural foodstuffs
   b. Produced in cooking
   c. Produced in stored food by microorganisms
2. Affecting formation of carcinogens in body
   a. Providing nitrates and secondary amines in the body
   b. Altering intake or excretion of cholesterol and bile acids
   c. Altering bacterial flora of the bowel
3. Affecting transportation, activation/deactivation of carcinogens
   a. Altering concentration in or duration of contact with feces
   b. Altering transport of carcinogens to stem cells
   c. Induction or inhibition of enzymes
   d. Deactivation or prevention of formation of short-lived intracellular species by use of vitamins, trace metals and other antioxidants.
4. Affecting promotion of cells
   a. Vitamin A deficiency
   b. Retinal binding protein
5. Over nutrition

Of the various factors discussed above, we are focusing on Items 2 and 3 from the above-mentioned list in this study.

Providing Substrates for the formation of carcinogens in the body

N-nitroso compounds are among the most powerful chemical carcinogens in laboratory animals, and this is a sign that it may be powerful even when produced in small amounts in humans. These compounds can be found in gastric juice, the digestive tract, or even in the infected bladder by products of a reaction between nitrites and certain nitrosable compounds. This nitrosation can be inhibited by the presence of antioxidants such as vitamin C in the stomach.

The problem with nitrites and nitrosable compounds is the fact that neither can be easily avoided in a diet. The compounds are abundant in fish and meat, but they may also be ingested as pesticide residues or drugs. In addition, nitrosable compounds may be formed in the colon from amino acids. Nitrite found in food may be derived from preservative color or a color and flavor enhancer. Nitrite may be formed in the salivary ducts, the hypoacid stomach, the infected bladder, and on nitrates or nitrogen in the gut by its bacterial action on nitrates. The most important source of nitrite is from nitrate, which is ingested in vegetables and also in water, but to a smaller extent.

Although much evidence has supported it, there is no definite answer as to whether certain types of cancer, such as cancer of the esophagus and stomach, correlates with nitrosamine formation (Armijo, 1981). Studies have shown that dietary nitrates, found mainly in vegetables, may actually protect the body against the development of certain types of cancer (Reddy, 1979).

Altering intake or excretion of cholesterol and bile acids

Certain fats might contribute to the production of carcinogens in the body by increasing the amounts of bile acids and cholesterol metabolites that encounter with the gastrointestinal tract. One study that compared the diets of Asians and Africans with the diet of people in the Western Hemisphere showed that larger amounts of the bile acids and cholesterol metabolites, especially deoxycholic and lithocholic acids, are found in those on a Western-type diet, and that, in comparison to Africans and Asians, colon cancer is also more common in Westerners (Curry, 2003). The amount of lithocholic and deoxycholic acids in humans can be increased by a high-fat, high-meat diet. When such a diet was tested on laboratory animals, there was an increase in the fecal excretion of bile acids and an increase in the incidence of colon cancer that was induced by various colon carcinogens, including methylnitrosourea. One study showed that bile acids fed or administered intrarectally for a long period to animals have a synergistic effect with small doses of carcinogens on the incidence of large intestine tumors (Greenlee, 2001).

The metabolic epidemiological data demonstrate a correlation between fecal bile acid metabolites and the risk for colon cancer in diverse populations (Reddy, 1980).  Such studies have shown that patients with colon cancer have a higher concentration of these metabolites in their feces than control patients.  A high intake of certain dietary fibers such as wheat bran and whole grain cereals which are rich in cellulose and hermicellulose leads to an increased stool bulk thereby diluting the colonic concentration of certain bile acids that accompany high levels of fat intake (Reddy, 1979). 

Doll and Peto (1981) examined the degree to which cancer incidence and mortality rates could be reduced in the United States.  Their choice of method stemmed from the observation that the cancer incidence rate among migrants tends to be found in the country to which they migrated, indicating that differential cancer incidence rates are due in part to environmental factors such as diet, exercise, occupational exposures, and smoking habits, and that the cancer does not arise exclusively because of genetic factors.  A follow-up study recognized the fact that given the major shift toward the regulation of occupational exposures to known carcinogens and the active surveillance of workers previously exposed to many of the carcinogens, the most modifiable component of cancer risk remains lifestyle factors (Monson, 1997). The American Cancer Society has certain risk factor assumptions on diet. These risk factors assume that prevalence of low levels of fruit and vegetable consumption will be reduced to 47-58% by 2010 and prevalence of high fat intake reduced to 9-15% by 2010 (Byers, 1999).

The strongest evidence of a relationship between diet and cancer has been related to the benefit of consumption of least five servings of fruits and vegetables per day. The probability of evidence is moderate for colon cancer.  Most of the research has focused on the effects of specific agents contained in fruits and vegetables such as carotenoids, selenium, folic acid, fiber, and Vitamins C and E. A study (Steinmetz, 1991) suggests that fruits and vegetables contain an anti-carcinogenic cocktail of substances, including both recognized nutrients and non-nutritive constituents. Together they inhibit the formation of carcinogens, reduce the capacity of transformed cells to proliferate, and act as antioxidants.

In studies, green vegetables and cruciferous vegetables seemed beneficial.  However, the prospective cohort studies to examine this relationship have yielded less conclusive findings (Voorips, 2000).  Vegetables contain so many beneficial vitamins and nutrients that it is difficult to identify which ones might be responsible for the possible association with colon cancer.  Fiber has received the most attention so far because of the proposed mechanism, i.e., fiber can help waste push through the colon more quickly so that colon is less likely to come into contact with the carcinogens.  However, recent study failed to support a link between fiber intake for over three years and the risk of the occurrence of colon polyps, the precursor lesion for colon cancer (Alberts, et al., 2000).

Colorectal cancer, while being a fervent killer, can be prevented with the right diet. Numerous studies have shown that a diet consisting of certain key nutrients plays a key role in preventing colorectal cancer. The three important factors of diet that include fiber, antotoxidants, and phytochemicals are present in vegetable and fruits. We consider vegetables and fruits in this study as an important portion of food consumption.

Fiber

Fiber, the structural part of plants that is indigestible by humans, is an element that can be found in grains, legumes, and fruits and reduces the risk of colon cancer. In 1989, researchers at the New York Hospital – Cornell Medical Center discovered that adding fiber to the diet could shrink pre-cancerous polyps that may have already begun to form in the colon.  Fiber has many advantageous uses to prevent cancer: it prevents chemicals form harming the colon’s lining; sweeps carcinogens through the intestines; and discourages the growth of harmful bacteria that could potentially lead to cancer, while encouraging the growth of good bacteria (U.S. National Cancer Institute, 2003). A study was conducted in India to compare the frequency of people infected with colon cancer and the amount of fiber people ate. North Indians tend to consume more fiber— roughage, cellulose, and vegetable fiber, in comparison to the South Indians. The studies also showed that the frequency of colon cancer was lower among the North Indians in comparison to the South Indians (Shamberger, 1984).

There are two types of fiber— soluble and insoluble fiber. While the soluble is useful in lowering blood cholesterol, the insoluble fiber is what studies have shown protects against colon cancer. This type of fiber can be found in fruits, vegetables, grains, and legumes. Two types of dietary fiber in general are known to help reduce colonic intraluminal pressure: cellulose and hemicellulose A and B. These sources of fiber are found especially in citrus fruits, carrots, and bran (Shamberger, 1984). Rich sources of fiber include whole wheat and bran cereals, bread, and pasta; legumes such as kidney beans, lima beans, and pinto beans; and fruits such as dried fruits and blackberries. Almost all other fruits, vegetables, and legumes like almonds and peanuts have a moderate amount of fiber. Fruits should be eaten with the skin in order to maximize the amount of fiber consumed (Winawer, 1995).

Dietary fat is known to promote colorectal cancer. No reason has been formally established in the role that fats play in relation to colorectal cancer, but many explanations have been offered. One such explanation states that fat increases the level of bile salts in the colon, which damage the lining of the colon and promote excessive cell growth that can lead to cancer. In order to prevent the occurrence of this cancer, it is most advisable to consume fat in moderation (Winawer, 1995).

Antioxidants

Antioxidants are a group of nutrients that counter the effects of molecules called free radicals, which are highly reactive substances that are byproducts of certain body functions and the body’s exposure to radiation, smoke, etc. Free radicals can lead to cancer by attacking a cell’s membrane and harming the DNA inside of the cell. They also interact with certain other substances in the body and turn those substances into carcinogens. Among the antioxidants, beta-carotene and Vitamine C are specific nutrients that help the body against colorectal cancer. Beta-carotene and Vitamin A specifically offer protection against colon cancer. They reduce the probability that altered cells will successfully change into a tumor (Shamberger, 1984). These nutrients are abundant in carrots, diary products, green and yellow vegetables and fruits such as peaches, mangoes, cantaloupes, and tomatoes. Vitamin C is believed to help protect the body against rectal cancer. It also strengthens the immune system, detoxifies compounds in the liver, and blocks the formation of nitrosamines in the digestive tract. Vitamin C is abundant in citrus fruits, potatoes, peppers, peas, kiwi fruits, spinach, asparagus, and strawberries (Winawer, 1995).

Vitamin D is another vitamin that may reduce the risk of colon cancer. It enables the body to absorb calcium, which is believed to inhibit colon cancer. Vitamin D is found in salmon, tuna, dairy products, and many fortified breakfast cereals (Winawer, 1995).

Phytochemicals

Phytochemicals are substances that help the natural defense system against cancer. Among these that directly help fight colorectal cancer are selenium and calcium. Calcium abundant in dairy products helps to neutralize the damage that bile and other cancer promoters may cause to the body. It also protects the colon’s lining from certain damaging substances in the stool. Studies have shown that people in Finland have a low rate of colorectal cancer cases particularly because of their high intake of dairy products.  Phytochemicals are abundant in fruits and vegetables such as those in the cabbage family (broccoli, cauliflower, brussel sprouts), garlic, onions, soybeans, and nuts (Winawer, 1995).  

Because vegetable and fruits contain the three dietary items discussed above that include fiber, antitoxidants, and phtochemicals, we will consider the effect of vegetables and fruits over meat consumption on colorectal cancer.

Effects of vegetables over meat on colorectal cancer in developed countries

Developed countries (DC) according the definition from the United Nations Web page are countries that generally have a per capita GDP in excess of $10,000.  Less developed counties (LDC) are mainly countries and dependent areas with low levels of output. Living standards, and technology; per capita GDPs are generally below $5,000 and often less than $1,500; however, the group also includes a number of countries with high per capita incomes, areas of advanced technology, and rapid rates of growth; includes the advanced developing countries, developing countries, Four Dragons (Four Tigers), and newly industrializing economies.

Even thought the food consumption patterns are different in these countries, there is a difference in the purchasing power of these countries.  Since meat is costlier than vegetables and fruits, developed counties generally have more access to meat and may therefore consume more meat than less developed countries. Since much of the research that we have identified in this study concerns the effects of vegetables and fruits on colorectal cancer, we will hypothesize the following:

H1. The effect of cancer incidence rates is positively associated with the affluence of a country.

H2.  The effect of vegetable and fruit consumption over meat consumption is negatively associated with cancer incidence rates.

 

Methods

The sample was drawn from various data sources.  The research question addresses how much vegetable, fruit, and meat consumption play a part in the cancer incidence rates in developed and less developed countries.  We collected sample data for 52 countries from the 150 developed and less developed countries. This was after dropping countries that did not have complete data available. The cancer incidence rates were drawn from GLOBOCAN2000 database. The population facts of countries were collected from the United Nations and World Factors and Figures Web site. The food consumption was drawn from the food balance sheet database from the United Nations Food and Agricultural Organization.  All data have been taken as an average between the years 2000 and 2001.

Variables

To determine the cancer effects of vegetable/fruit to meat consumption, the dependent variable CANCR was computed as cancer incidence rates, i.e., the number of cancer incidences per population in various countries.  The vegetable and fruit consumption was compared to the meat consumption in various countries.  The ratio of total vegetable and fruit consumption per population to meat consumption per population was included as the variable VFMEAT.  The total consumption of food TFC in these countries was also included as one of the independent variables.  To understand the effects on the developed and less developed counties, we controlled the analysis by using the variable GDP that is the Gross Domestic Product per population. 

Results

Certain preliminary steps were taken in order to assure that a linear regression test could be conducted. A scatter plot and residual plot were observed. The scatter plot for the first hypothesis tested, where CANCR was the dependent variable and GDP was the independent variable, had a correlation value of 0.846. Although the data does have some outliers, the 0.846 correlation shows that the linear relationship between the two variables is positive and very strong. Similarly, a scatter plot between the CANCR and VFMEAT variables shows a strong, negative correlation value of –0.634. By looking at the residual plots for both tests, one can see that variation about the 0 is approximately even throughout the given data, and that no detectable pattern is present. All of this supports a linear regression test being conducted.

After the linear tests were conducted, the results for the first test comparing CANCR and GDP showed an R² value of 0.716 and a p-value of 0.009. The R² value is high, simply stating that 71.6% of the variation in the variable CANCR is explained by the regression. For this experiment, an alpha level of 0.05 was chosen, and the p value of 0.009 is less than that alpha level. Because it is smaller than the noted significance level, the p-value is significant. This means that such an extreme value as what was tested cannot occur due to chance alone. The results for the second test comparing VFMEAT and CANCR had a R² value of 0.744 and a p-value of 0.029. This R² value is also high, where 74.4% of the variation in the dependent variable CANCR is explained by the regression. The p-value of 0.029 is less than our chosen alpha level of 0.05, thus making it a significant value.

Discussion

The means, standard deviations, and correlations are reported in Table 1. The p-values of 0.009 and 0.029 are less than the standard 0.05 value, and so there is enough evidence to accept our hypotheses. We find a positive association between cancer incidence rates and the affluence of a country and a negative association between vegetable and fruit consumption over meat consumption and cancer incidence rates.

Therefore, we can conclude that the more developed countries have a higher rate of colorectal cancer and that as the ratio between vegetable and fruit consumption over meat consumption increases, the cancer rate in a population decreases. This concurs with the research discussed earlier (Curry, 2003). 

 

Table 1

Descriptive Statistics and Correlations

	Variable	Mean	Std. Deviation	N	CANCR	TFC	VFMEAT
Total Food Consumption per population	TFC	135518.5	580015.6	52	0.042
Vegetable and Fruits to Meat Consumption	VFMEAT	5.369817	4.991188	52	-0.634	-0.151
GDP/per capita	GDP	13966.2	9968.778	52	0.846	0.054	-0.590

 

These results are in concurrence with the overall subjective view that vegetable and fruit consumption helps to reduce the effects of cancer.  This also acknowledges that higher vegetable and fruit consumption compared to meat consumption reduces cancer incidence rates.

We highlight several implications for future research.  This study needs to be extended to the rest of the developed and less developed countries as well.  We have considered average values for food consumption and cancer incidence rates.  Further research can use values for a number of years and analyze the effects.  The study can be extended to the least developed countries as well.

 

References

Alberts, D.S., et al. 2000.  “Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas,” New England J. Med. 342(16):1156-1162.

American Cancer Society, Cancer Facts and Figures 2002.  Atlanta.

Armijo, R. 1981. Int. J. Epidemiol. 10(57).

Atwater, W.O. and Benedict, F.G. 1899.  “Experiments on the Metabolism of Matter and Energy in Human Body,” U.S. Dept. Agriculture Bull. No. 69, Washington, D.C.,

Atwater, W.O. and Bryant, A.P. 1906. “The Chemical Composition of American Food Materials,” U.S. Dept. Agriculture Office of Experimental Stations Bull. No. 28, (Revised).

Bjelke, E. 1978.  “Dietary factors and epidemiology of cancer of the stomach and large bowel.  Aktul Ernaehrungsmed.” Klin. Prax. Suppl. 2:10-17.

Byers, T. et al. 1999.  “The American Cancer Society challenge goals.  How far can cancer rates decline in U.S. by the year 2015?”  Cancer, 86(4): 715-727.

Chick, H. et al. 1923.  “Studies of Rickets in Vienna 1912-1922,” Spec. Rep. Ser. Med. Res. Coun. No. 77, HMSO, London.

Cuello, P. et al., 1976. Journal of National Cancer Institute, 57(1015).

Curry, S.J., et al. 2003.  “Fulfilling the Potential of Cancer Prevention and Early Detection,” The National Academic Press, Washington D.C.

Doll, R. and Peto, R. 1981. “The causes of cancer: quantitative estimates of available risks of cancer in the United States today,”  J. Natl. Cancer Inst.  66(6): 1191-1308.

Edgerton, V.R. et al. 1982. “Iron Deficiency: Brain Biochemistry and Behavior,” New York, Raven, pp. 141-160.

Ge, K in M. Winick, Ed., 1982.  Adolescent Nutrition, New York, Wiley, pp. 127-138.

Greenlee, R.T. et al. 2001. “Cancer Statistics, 2000,”  CA Cancer J. Clin. 50(1): 7-33.

King, C.G. and Waugh, W.A. 1932.  Science, 75(357).

Klevay, L.M. et al.  1980. Clinical Research, 28(758A).

Klevay, L.M. et al.  1982.  Clinical Research, 30(780A).

Mahaffee, K.R. et al. 1982.  New England Journal of Medicine, 307(573).

Monson, R.R. and Christiani, D.C. 1997.  “Summary of the evidence: occupation and environment and cancer.”  Cancer Causes Control, 8(3): 529-531.

Osborne, T.B. and Mendel, L.B. 1913.  Journal of Biol. Chem., 15(311).

Pollitt, E. et al. 1982. “Iron Deficiency: Brain Biochemistry and Behavior,” New York,

Prasad, A.S. 1982.  Ed., “Clinical, Biochemical, and Nutritional Aspects of Trace Elements,” New York, Alan R Liss, 1982.

Preventcancer.org. 2003 Aug 3. Colorectal Cancer Statistics  http://www.preventcancer.org/colorectal/press/2k2statistics.cfm

Reddy, B.S. 1979.  Advanced Nutrition Research, 2(199).

Reddy, B.S. et al., 1980.  Advanced Cancer Research, 32(237).

Rickes, et al. 1948.  Science, 107(396).

Sandstead, H.H. 1984. “Trace Metals in Human Nutrition,” Edited by Winick, Myron.  “Nutrition in the 20^th Century,” John Wiley & Sons, New York.

Sandstead, H.H. et al. 1982. “American Journal of Clinical Nutrition,” 36(1046).

Schroeder, H.A. et al. 1970.  Journal of Chronic Diseases, 23(1230).

Shamberger, R.J. 1984.  Nutrition and Cancer.  Plenus Press, New York: 37-41.

Shamberger, Raymond J. Nutrition and Cancer. New York, NY: Plenum Press, 1984.

Smith, M.I. and Hendrick, E.G. 1926.  Pub. Health Rep. Washington, 41(201).

Steenbock, H. 1919.  Science, 50:352.

Steinmetz, K.A. and Potter, J.D. 1991.  “Vegetables, fruit and cancer. II. Mechanisms,”  Cancer Causes Control 2(6):427-442.

Szent-Gyorgyi, A. 1928. Biochem. J., 22(1387).

U.S. National Cancer Institute. What You Need To Known About Cancer of the Colon and Rectum. 2 Aug. 2003.  http://www.cancer.gov/cancerinfo/wyntk/colon-and-rectum

Vallee, B.L. et al. 1983 “Biological Aspects of Trace Elements,”  New York, Raven.  pp. 1-14.

Voorrips, L.E. et al. 2000.  “Vegetable and fruit consumption and risks of colon and rectal cancer in a prospective cohort study:  The Netherlands Cohort Study on Diet and Cancer,” American J. Epidemiol. 152(11): 1081-1092.

Weisburger, J.H. and Horn, C.  1982.  Bull.N.Y. Acd. Med., 58(296).

West, R. 1948.  Science, 107(398).

Winawer, Sidney J., M.D., et al. Cancer Free: The Comprehensive Cancer Prevention Program. New York, NY: Simon & Schuster, 1995.

Wynder, E. L. 1984. “Nutrition, Diet and Cancer – an Evaluation,” Ed. by Winick, Myron.  “Nutrition in the 20^th Century,” John Wiley & Sons, New York.

 

 

[1] This research study was conducted under the guidance of Chrislyn D’Souza-Schorey, Department of Biological Sciences, Notre Dame University, Indiana.