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66 Cards in this Set
- Front
- Back
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What is cancer and carcinogenesis?
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• Cancer is the unchecked proliferation of tissues originating from a single transformed cell. Carcinogenesis is the term used to describe the development of cancer, which occurs in several stages. Examples of response to specific dietary interventions exist for all stages of carcinogenesis
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What are the stages of cancer development?
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• Initiationpromotionprogressionmetastasis
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What is the role of a genetic mutation in carcinogenisis?
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• A single mutation may generate a clone of cells that grow faster or survive longer than normal cells. When one of these altered cells mutates again, it can give rise to more advanced premalignant cells. Repetition of this process may then lead to the emergence of a cell clone with full cancer phenotype
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Describe the initiation stage of cancer.
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• Initiation occurs upon exposure of the DNA within cells to ionizing radiation, biological agents, or chemical mutagens. Cancer cells often arise from distinctly altered but non-cancerous cells
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Describe the promotion Stages of Cancer.
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• Promotion encompasses the early tumor growth period. More mutations allow the transformed cell to bypass growth controls, escape programmed cell death and evade destruction by immune cells
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Describe the progression Stages of Cancer.
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• Further progression leads to a malignant tumor with destructive growth. During this stage, tumor growth may be slowed by hormonal factors and the body’s immune defenses
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Describe the metastasis Stages of Cancer.
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• Metastasis occurs when tumors spread beyond the normal confines of their tissue of origin, sometimes to distant organs
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How do dietary and Lifestyle Factors affect cancer development?
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• Smoking, food choices and other lifestyle factors influence all stages of carcinogenesis. 50-70% of overall cancer risk is related to habitual food intake, body composition and exercise patterns. Dietary and lifestyle interventions seem to be most effective during the earliest stages of cancer development. The impact on invasive growth of advanced cancer and its spread to distant tissues is much more limited.
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How does Abnormal Protein Expression cause cancer?
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• DNA translates into proteins that are essential for normal cellular activity. Mutations often change the rate at which the affected gene is translated to its functional protein and may allow cells to grow at a faster than normal rate. Since all tumor cells carry the same mutation, the change in molecular behavior affects all of them.
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Which Genes are related to Cancer?
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• Mutations in numerous different genes can contribute to the transformation of cells. Such mutations cause malignancy only in combination, usually together with defects in additional genes
Tumor Suppressor Genes Proto-oncogenes Mutator Genes p53 K-ras MSH2 APC c-MYK MLH1 BRCA1 HER2 NF1 RET • Each of these classes of genes play an important role in the control of cellular growth promotion, growth inhibition and apoptosis induction. Damaged tumor suppressor genes contribute to cell transformation by removing their normal inhibition of growth. Mutations of proto-oncogenes can increase the growth-promoting activity of these critically important genes. Defective mutator genes reduce the ability of cells to prevent or repair damage to these and other cancer-related genes |
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How do Free Radicals affect cancer?
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• Oxidative reactions generate free radicals as a by-product. Free radicals carry an extra electron, indicated by the dot next to the chemical formula. Free radicals react readily with proteins, DNA, and lipids
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What are some major Free Radicals in the Human Body?
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• Free radical molecules have one or two unpaired electrons
• The major oxygen free radicals in the human body are o Superoxide anion Formed in oxidizing reactions (such as xanthine oxidase) and by ionizing radiation Converted to hydrogen peroxide by superoxide dismutase (SOD) o Hydrogen peroxide Formed from superoxide anion by SOD or by oxidative reactions Converted into oxygen and water by catalase and peroxidases o Hydroxyl radical Non-enzymatically formed from superoxide anion or hydrogen peroxide in the presence of iron or copper This is the most genotoxic oxygen free radical |
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How is Free Radical Generated?
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• Free radicals can attack cellular membranes
• Free radical generation is a necessary process as part of the body’s defense system. However, when antioxidant defenses are lowered, these free radicals can damage the lipids and proteins in cell membranes |
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What are some enzymes and antioxidants that can help curb the effect of free radicals?
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o Enzymes (cytosol)
Superoxide dismutase Catalase Glutathione peroxidase (contains selenium) o Fat-soluble antioxidants (membranes and lipoproteins) Tocopherols Carotenoids o Water-soluble antioxidants (cytosol and body fluids) Ascorbic acid Uric acid (from nucleic acid metabolism) |
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How does ascorbic acid (vitamin C) help deal with free radicals?
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• Reactivation of alpha-tocopherol by ascorbic acid
• Once alpha-tocopherol has reacted with a free radical, it becomes a pro-oxidant itself (tocopherol quinone). It can be reactivated back to alpha-tocopherol with the help of ascorbic acid. Tissue enzymes then have to reactivate the resulting ascorbyl free radical. These relationship emphasize the synergism of different nutrients for antioxidant defense and the potential harm from excessive intake |
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How are DNA adducts formed?
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• DNA + (polycyclic aromatic hydrocarbons, heterocyclic amines, nitrosamines, aflatoxins) = DNA Adduct
• The term “DNA adduct” is used to indicate that molecules are covalently attached to some of the bases of DNA. DNA adducts may be formed upon exposure of DNA to a wide range of food-borne carcinogenic compounds |
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How is nitrosamine formed?
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• Protein amino acids + nitrite nitrosamine
• When proteins or amino acids are exposed to nitrite, nitrosamine compounds may form. Many processed meat, poultry and fish products contain nitrite as a preservative. Another source is the conversion of nitrate to nitrite by intestinal bacteria. Vegetables grown with excess nitrate fertilizer may contain significant nitrate amounts • The presence of ascorbic acid (Vitamin C) inhibits nitrosamine formation. People with high fruit and vegetable consumption have lower cancer risk |
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How can charbroiling cause an Increased Cancer Risk?
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• Cooking adds attractive flavors to meat, poultry, and fish. Charring generates polycyclic compounds. Frying or broiling of creatine-containing meats produces heterocyclic amines. When fat drips on hot coals, the carcinogen-rich smoke can contaminate exposed foods. Both polycyclic aromatic hydrocarbons (PAH) and hterocyclic amines (HA) from DNA adducts and may cause mutations giving rise to cancer.
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Are Carcinogens present in Smoked Foods?
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• Smoked meats, poultry, and fish contain many carcinogenic polycyclic aromatic hydrocarbons.
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What is Dietary Fiber’s role in preventing cancer?
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• Dietary fibers may play a protective role against carcinogenesis
• Mechanism: o Bind polycyclic aromatic hydrocarbons and potential carcinogens o Shorten transit time o Act as bulking agent to reduce carcinogen concentration acting on intestinal mucosa • Examples o Apples, green beans, whole wheat bread • Dietary fibers are the indigestible carbohydrate components of plant foods. Recommended daily intake of fiber is 25g for women, 38g for men, slightly less for people over 50 years of age |
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What are the two groups of enzymes that act on ingested compounds?
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• The potency of ingested carcinogens greatly depends on their metabolism in the liver. Two groups of enzymes act on ingested compounds (carcinogens) that don’t contribute to the nutriture or metabolism
o Phase I enzymes activate carcinogens, mainly by hydroxylating them o Phase II enzymes conjugate the activated compounds and promote their excretion • Higher phase I enzyme activity generally increases DNA adduct formation; higher phase II enzyme activity decreases DNA adduct formation |
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How are Carcinogens activated?
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• Phase I enzymes in the liver activate carcinogens such as the nicotine derived compound NNK. This group of carcinogen-metabolizing enzymes includes cytocrhome p450 enzyme family and other microsomal hydroxylases and oxidases. Alcohol, barbiturates, and other compounds can induce phase I enzyme production, accelerating carcinogen activation, and increasing the likelihood of DNA adduct formation.
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How are DNA Adduct’s formed?
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• Formation of DNA adduct by “activated” (i.e. hydroxylated) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).
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How are DNA Adducts replicated?
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• DNA transcription of chemically modified bases, so-called DNA adducts, tends to incorporate non-complimentary bases into the new strand. Such mismatching of bases during replication introduces DNA mutations.
• The diagram shows what happens during replication of a DNA strand exposed to a DNA-modifying carcinogen: the chemically modified DNA base pairs with the wrong base. The new strand now carries an altered DNA sequence and the old strand still contains the DNA adduct |
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How are carcinogen’s eliminated?
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• Phase II enzymes in the liver and intestines prepare the detoxification of many natural and synthetic chemicals, including many potent carcinogens such as the nicotine-derived compound NNK. Important phase II enzymes include glutathione S-transferases, glucuronidases and NADPH quinone reductase. All of these enzymes tend to improve water solubility of their carcinogen substrates and promote their excretion into bile or urine.
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What are some Phase II Enzyme Inducers?
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• Many fruits and vegetables contain compounds that activate phase II enzymes. Activation of phase II enzymes helps to detoxify and excrete carcinogens more rapidly. Broccoli, cauliflower, cabbages, cress and radishes contain isothiocyanates, which are potent phase II enzyme inducers. Garlic, onions, and leeks contain similarly effective organosulfur compounds. Plant enzymes generate the active compounds only when the cells are crushed. The sharp taste of the fresh vegetable indicates its content of phase II enzyme-inducing phytochemicals. Baked whole garlic tastes sweet and contains little of the active compounds, because the enzymes for their production have been inactivated during the cooking process.
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How is the normal balance of growth promotion and inhibition upset?
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• Changes in either proto-oncogene or tumor suppressor gene expression upset the normal balance of growth promotion and inhibition
• Tumor suppressor genes o Expression increases mainly in response to cell cycle signals or irreversible DNA damage • Proto-oncogenes o The products of these genes often trigger mitogenesis or participate in signal transduction |
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How is growth restricted at the molecular level?
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• Specific cell signals as well as DNA damage activate tumor suppressor gene expression, which may stop cell division (cell cycle arrest) or trigger programmed cell death (apoptosis)
• p53 and other tumor suppressor genes limit unrestrained cell proliferation • Many cancers have one or more defective tumor suppressor genes. To promote cancer, usually both copies of the tumor suppressor gene in a particular cell have to be inactivated |
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How is growth promoted at the molecular level?
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• Proliferation and differentiation are stimulated by growth factors and hormones that bind to specific receptors in the cell membrane and trigger a cascade of down-stream signaling
• Regulatory GTP hydrolases mediate cell signaling • Growth factors binding to a cell activate the RAS-derived G proteins. These regulatory GTP hydrolases can mediate signaling for a short while after activation and then revert to the inactivated state again. They mediate signaling only when farnesyl side chains anchor them to the cell membrane |
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How is Abnormal Growth Promoted?
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• Many proto-oncogenes are critical elements of cell signaling cascades, whose mutated forms (oncogenes) cause excessive or persistent growth stimulation
• Variant GTP hydrolases can cause persistent signaling • A RAS gene is mutated in 20-30% of all human cancers. Most of these gene variants encode G proteins that tend to remain longer in the activated state and therefore cause inappropriately high signaling |
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Dietary Proliferation Modulators
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• A wide range of natural compounds in plant-derived foods is likely to affect cancer risk through diverse mechanisms. The disruption of abnormal persistent signal transduction may contribute significantly to the beneficial effects of many fruits
• Regular consumption of generous amounts of fruits and vegetables appears to reduce the risk of many cancers and in particular slow the growth of smaller precancerous and cancerous lesions |
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What is G Protein Anchoring?
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• Post-translational modifications target G-proteins to the cell membrane. Effective signal transduction occurs only when the receptor and its G-protein are held in proximity. Farnesyl side chains added during protein synthesis are important to anchor the G-protein to the cell membrane and ensure effective signal transduction.
• Compounds in some fruits inhibit with the formation of G protein anchors and may reduce cancer risk by disrupting excessive signaling in precancerous and cancerous tissue with activating RAS mutations. |
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What are some examples of Plant Anticarcinogens and how do they work?
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• Monoterpenes and polyphenols from fruits and vegetables can inhibit excessive tissue proliferation by limiting persistent G-protein activation
• Some monoterpenes and other plant chemicals are very effective anticarcinogens in cell culture and animal models. Ongoing investigations in humans will have to determine which of these and other phytochemicals actually prevent cancer |
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How does Nutrition give Protection against Cancer?
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• It is the nature of tumor cells to multiply more rapidly than normal cells. The tumor cells may eventually break through tissue barriers and spread to other organs. In most cases, however, nascent tumors are contained and eliminated through various processes that include programmed cell death, hormonal control and immune surveillance. Tumors expand when they continue to be exposed to growth-stimulating factors and when apoptosis and immune-mediated culling of abnormal cells fails. Nutritional status and dietary exposure strongly adds to genetically determine processes regulating cell growth. Both essential nutrients and non-essential food constituents can either slow or accelerate tumor expansion, particularly during the early stages of tumor development.
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What are examples of Hormone-like Vitamins and how do they work?
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• The activated metabolites of vitamin A and vitamin D have hormone-like actions that parallel in some ways those of estrogen and other steroid hormones. They all form complexes with specific binding proteins, called nuclear receptors. The hormone-receptor complex then acts on specific genes.
• Vitamin A is the precursor of retinoic acid. Retinoic acid and the retinoid X receptor (RXR) form a complex, which can activate or silence specific genes in the cell nucleus. The RXR-RXR complex promotes cell differentiation and induces cell cycle arrest. Also, most steroid hormones function only as part of mixed dimmers that include the retinoic acid-RXR complex. • Vitamin D is the precursor of 1,25-dihydroxyvitamin D which binds to the vitamin D receptor (VDR). This complex then combines with RXR to form the functional dimeric complex • Inadequate intake of either vitamin A or vitamin D has been found to increase cancer risk. Use of retinoic acid and chemically modified derivatives of vitamin D have shown great promise for chemoprevention in high-risk individuals • Nuclear receptors mediate the vitamin effects on genes controlling proliferation and differentiation • Very high retinol intake, of 10 or more times the current recommended dietary allowance (RDA), increases cell proliferation and increases the risk of fetal malformation during early pregnancy |
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What are the Dietary Effects of Estrogen?
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• Estrogen promotes the proliferation of many cell types, particularly in breast, ovaries and prostate. Early infancy and puberty are particularly critical periods during which exposure of budding breast ducts to high estrogen concentration sets the stage for the development of cancer later in life.
• Several diet-related factors can raise estrogen levels, including o High intake of fat, particularly of saturated and trans fat o High body fat (particularly during puberty) o High alcohol consumption (more than one drink/day) • These dietary factors lower estrogen levels modestly o High consumption of whole grains o High intake of fruits and vegetables • Women who have more than one alcoholic drink/day have about 20% higher estradiol concentrations in blood than women who don’t consume alcohol |
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What are the benefits of Phytoestrogens?
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• Many fruits and vegetables contain natural plant compounds called phytoestrogens because of their estrogen-like properties. Phytoestrogens typically are flavonoids, which means that they are variations of conjugated ring structures with similarities to estrogen. Soy beans are a particularly rich food source of genistein and structurally related phytoestrogens. Other legumes also contain small amounts of these isoflavones, a subclass of the flavonoids.
• Phytoestrogens can bind to estrogen receptors, but elicit much weaker responses. In people with low endogenous estrogen concentration, phytoestrogen consumption may increase estrogen-related effects. But in people with high estrogen levels, they may act as competitive inhibitors and reduce estrogen-related effects. • Estrogen promotes the growth of many tumors in breast, ovaries, prostate and other tissues. Competition of phytoestrogens with endogenous estrogen may be beneficial for people with such hormone-sensitive cancers. This may explain in part the protective effects of phytoestrogen-containing fruits and vegetables. • Many consumers are concerned about steroids and growth hormones in their meats and dairy products, and how these may increase their cancer risk. You should know that the amounts from such foods are much smaller than the doses needed to enhance tumor progression in the most susceptible laboratory animals |
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What is Immune Surveillance?
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• Nutritional status influences progression and metastasis of malignant tumors
• Dietary factors that tend to strengthen immune function include the following o Low-energy diet o Low-fat diet o High omega-3 to omega-6 fatty acid ratio o Adequate intake of vitamins and carotenoids o Adequate, but not excessive intake of trace minerals including zinc and selenium |
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How does overnutrion influence cancer risk?
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• Chronic overnutrition promotes a cycle of obesity and hyperglycemia that can lead to diabetes
• The metabolic and hormonal profile that results from an oversupply of nutrients increases the activity of mitogens, such as insulin-like growth factors • Obesity is associated with a higher risk of developing several cancers o Colon o Breast o Endometrium o Kidney o Esophagus |
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What are some Metabolic consequences of overnutrition?
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• Obesity promotes hyperglycemia and insulin resistance, which trigger increased insulin production. Obesity also increases estrogen levels
• Increased levels of insulin may promote carcinogenesis by increasing exposure to IGF-I |
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What are Insulin-Like Growth Factors?
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• Insulin-like growth factors, IGF-I and IGF-II, function as potent mitogens with critical roles in embryonic and fetal development. IGF-I also mediates cell proliferation and differentiation in adulthood. Both negatively regulate apoptosis. Circulating levels of IGF-I may increase in response to obesity and hyperglycemia
• IGF-I o Expressed primarily in the liver o Stimulated by growth hormone o Serum levels in adults: 100-200 ng/ml • IGF-II o Widespread expression o Imprinted gene o Serum levels in adults: 400-600 ng/ml • The IGF family consists on two peptide ligands, to receptors, and six binding proteins (IGFBPs) • Links to prostate and colorectal cancers o Increased risk associated with high circulating levels of IGF-I o Inverse association with IGFBP3 (binds ~90% of circulating IGF-I and exerts ligand-independent antimitogeneic and proapoptotic effects) • The bottom line: overnutrition, leading to obesity and hyperglycemia, promotes exposure to the mitogenic activity of IGF-I, which ultimately elevates cancer risk |
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What is the goal of Nutritional Cancer Prevention?
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There is little doubt that properly targeted nutritional changes can reduce cancer risk and support the treatment of cancer patients. It is critical to know which eating patterns are helpful and how to help patients to achieve change
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What are the Dietary Guidelines for a person?
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This is the Complete Nutrition and Physical Activity guide of the American Cancer Society
Maintain a healthy weight throughout life Balance caloric intake with physical activity Avoid excessive weight gain throughout life Achieve and maintain a healthy weight if overweight or obese Adopt a physically active lifestyle Adults: engage in at least 30 minutes of moderate to vigorous physical activity, above usual activities, on 5 or more days of the week; 35-60 minutes of intentional physical activity are preferable Children and adolescents: engage in at least 60 minutes per day of moderate to vigorous physical activity at least 5 days per week Eat a healthy diet, with an emphasis on plant sources Choose food and beverages in amounts that help achieve and maintain a healthy weight Eat 5 or more servings of a variety of fruits and vegetables each day Choose whole grains in preference to processed (refined) grains Limit consumption of processed and red meats If you drink alcoholic beverages, limit consumption Drink no more than 1/day for women or 2/day for men |
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How does one Use MyPyramid?
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Questions to ask
Do you eat food from each of the food groups daily? Advice: consume multiple food from each food group daily How often do you eat each day? Advice: ensure plentiful fruit and vegetable consumption What beverages do you drink each day? Advice: Moderate alcohol intake Are you taking any nutritional supplements? Advice: avoid excessive nutrient supplementation These guidelines are based on a 2000 calorie pattern Grains: 6oz (180g) a day, at least half of which is whole grains; 1oz (30g) = 1 slice of bread, 1 cup of cereal, or ½ cup of cooked pasta or rice Nutrients provided: carbohydrate, dietary fiber, vitamins, minerals, phytochemicals Vegetables: 2 ½ cups per day; note that a 2-cup serving of raw leafy greens counts as 1 cup from the vegetable group Nutrients provided: vitamins, minerals, fiber, phytochemicals Fruits: 2 cups per day; eat a variety of fruit; limit fruit juices; ½ cup of dried fruit = 1 cup from the fruit group Nutrients provided: vitamins, minerals, fiber, phytochemicals Oils: 6 teaspoons a day; limit extras – solid fats and sugars – to 265 calories a day Nutrients provided: some fats provide essential fatty acids and vitamin E Milk, yogurt, and cheese: 3 cups (720ml) per day of calcium-rich foods; choose low-fat or fat-free; 1.5oz (45g) of natural cheese or 2oz (60g) of processed cheese = 1 cup from the milk group Nutrients provided: calcium, protein, potassium, vitamin B12, vitamin D Meat and Beans: 5 ½ oz (165g); choose low-fat or lean meats and poultry; vary your protein routine; ¼ cup cooked, dry beans, ½ oz (15g) nuts or seeds, 1 Tbsp peanut butter, or 1 egg = 1 oz (30g) Nutrients provided: high quality protein, iron, vitamin B12 |
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What are some Foods for Cancer Prevention?
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Many compounds in foods are known to influence cancer development at one or more of the stages
Preventing or slowing cancer development Isothiocyanates and indoles in cruciferous vegetables Sulphur compounds in onions, garlic and chives Flavonoids in berries and many other fruits Isoflavones in soy products Insoluble dietary fiber in whole grains, bran and vegetables Furthering cancer development Heme and iron in red and processed meat Saturated fat in meats, fatty cheese and butter Trans ft in commercial fried or baked goods Calories from starchy, sweetened and fatty foods Ethanol in alcoholic beverages |
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What are Cruciferous Vegetables?
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Characteristics of cruciferous vegetables
Members of the brassica family (e.g. cabbage, cauliflower, broccoli, cress, radishes, turnips) Named for their cross-shaped blossoms Contain anticarcinogenic compounds (e.g. indoles and isothiocyanates) Isothiocynates may reduce cancer risk by activating phase-II enzymes and thereby enhancing the detoxification of carcinogens A good strategy for preventing cancer should include the regular consumption of cruciferous vegetables |
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How does one Reduce Fat Intake?
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High fat intake or high calorie diets appear to have an association with the development of colon, breast, prostate, and ovarian cancers. Reducing fat intake will automatically reduce calorie intake and have other health benefits
Compare the number of fat grams and calories per serving of the following foods Calories Fat (grams) 8 oz steak 680 48 3 oz steak 255 18 Chocolate cheesecake 257 16 Angelfood cake 161 0.1 8 oz whole milk 150 8.0 2% milk 121 4.7 Skim milk 86 0.4 Small bag of regular potato chips 150 9.6 Small bag of baked potato chips 130 2.0 |
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What is the importance of Dietary Fiber?
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Soluble (gums, pectin)
Effect: form gel with water, bind bile acids Sources: fruit, vegetables, legumes, bran Insoluble Cellulose, hemicellulose Effect: promote microbial growth, soften stool Sources: grains, bran, vegetables, legumes Lignin Effect: bind bile acids, reduce their reabsorption Sources: seeds, nuts, broccoli stems Lignan Effect: metabolites have estrogen-like properties Sources: grains, bran, seeds Recent research suggests that high fiber consumption protects less against colorectal cancer than previously thought. On the other hand there is increasing evidence for a protective effect of fiber from grains against breast cancer, particularly in premenopausal women. Some of the observed protection of grains and seeds against colorectal and other cancers may be related to the estrogen-like properties of lignan breakdown products (phytoestrogens). Remember, however, that there are other well-established health benefits of vegetables, grains and other fiber-rich food which include lower cardiovascular disease risk and more regular bowel movements. |
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What are some good reasons to promote getting nutrients from foods rather than pills?
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Good reasons to promote getting nutrients from foods rather than pills
Many compounds may work in a synergistic relationship in food whtat will not be found in pills Toxicities and nutrient imbalances are less likely to occur when nutrients are derived from foods There may be anticarcinogenic compounds that are yet undiscovered and are only found in natural substances, e.g. fungi, plants, animals High intake of some nutrients may decrease the absorption of others Food offer more than anticarcinogenic substances – the substrates of protein, carbohydrate, and fat provide energy and tissue building capabilities Compounds isolated into pill form can be easily overdosed with potentially dangerous side effects; they can also cause harmful interactions with medications and other aspects of medical care |
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What are Carotenoids?
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• Carotenoids, including members of the provitamin A group, have antioxidant properties (singlet oxygen quenching and peroxyl radical scavenging) and are thought to reduce the development of epithelial cancers, especially of the lung, bladder, mouth, and larynx
• Lycopene, a carotenoid with no provitamin A activity, quenches singlet oxygen more effectively than does beta-carotene, the best-known provitamin A compound • Lutein, present in the human macula and retina, filters blue light and quenches and scavenges photo-induced reactive oxygen species • Food sources of carotenoids o Beta-carotene: dark green, yellow, and orange fruits and vegetables o Lycopene: red vegetables and fruits o Lutein: green leafy vegetables |
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Why is Vitamins C, E and Selenium important?
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A varied diet that contains fruits, vegetables, nuts, meats, seafood, and grains will provide ample amounts of these important antioxidants
Vitamin C Functions: acts as a nitrite scavenger Dietary sources: citrus fruits, strawberries, kiwi, potatoes, cabbage Vitamin E Scavenges free radicals Dietary sources: vegetable oils, nuts Selenium Promotes the action of glutathione peroxidase, a hydrogen peroxide scavenger Dietary sources: meats, seafood, cereals and grains You can use selenium as an example when explaining the uselessness of megadoses to your patients: selenium activates glutathione peroxidase; once the enzyme is saturated, more selenium will have no additional effect |
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What is Folate?
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The B vitamin folate participates in several critical metabolic pathways that are important for DNA synthesis and methylation
Transfer of one-carbon groups Biosynthesis of purines Transfer of methyl groups High folate intake appears to be associated with decreased cancer risk. Lack of folate in the diet could contribute to the development of cancer by impairing DNA repair or by promoting aberrant DNA methylation, which could alter gene expression Good food sources of folate Leafy, green vegetables Citrus fruits and juices Dried beans • Fortification of the food supply with folate was approved by the FDA in 1996 to prevent neural tube defects in the developing fetus |
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What are some Epidemiological Studies of diet cancer relationships?
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Basic design for epidemiological studies of diet-cancer relationships
Ecological: comparison on food-disease relationships between very large groups (countries) Case-control study: comparison of food consumption between groups of affected and non-affected individuals Prospective cohort study: comparison of outcome measures over time of differently exposed individuals Controlled trial: comparison of outcome measures between groups adhering to a narrowly focused intervention |
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What is an Ecological Study?
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How to do it: collect and correlate data on dietary habits and disease from people living in different regions, states, or countries
Example: per capita consumption of cabbage in different countries was related to mortality rates from colorectal cancer. People in countries with high cabbage consumption had lower mortality rates. |
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What are some Advantages/Disadvantages of Ecological Studies?
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• Advantages
o Often can make use of existing data, reported in the literature or from observations on file • Disadvantages o The quality of food consumption data often is poor, because the data have not been controlled for scientific purposes. The method for detecting or reporting disease often differences between countries. There is little opportunity to control for other factors that influence diet-cancer relationship (cofounders), because individual data are not available • What you need to know o Ecological studies are valuable to identify dietary habits and practices that can help in cancer prevention. However, this is the weakest type of epidemiological study and should be used for hypothesis finding only. Beware of confounding factors! |
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How is a Case Control Study done?
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How to do it: select patients who have the disease of interest; select a group of controls that is similar to the patient group in most respects (gender, age, race). Compare past dietary habits of patients and controls
Example: a case-control study compared dietary habits of patients with colon cancer and of healthy people from the same area in Greece. The cancer patients were more likely to eat meat regularly, but ate less cabbage, lettuce and other vegetables |
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What are some Advantages/Disadvantages of Case-Control Studies?
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• Advantages
o Results can be obtained very rapidly, because there is no delay to wait for the disease to occur • Disadvantages o Once patients know of their diagnosis they tend to change their diet; they may also report their previous dietary habits differently. Cancers usually develop many years prior to diagnosis and a reliable account of all relevant exposures may not be obtained • What you need to know o Case-control studies are a very cost-effective means to get rapid answers to urgent questions. However, even if a particular dietary habit helped prevent the disease in controls this may not work today because circumstances may have changed since then! |
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How does Frequency of Consumption affect carcinogens
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100 cases of histologically confirmed cancer of the large bowel, 100 controls matched to each index case for sex and age (+/- 5 years), all from the same geographically constrained area in Greece. Interview asks for average consumption of foods prior to onset of the disease.
Relative risk associated with increasing the frequency of consumption of certain food from once to twice a week Beef = 1.77 Cabbage or lettuce = 0.76 |
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How does one do a Prospective Cohort Study?
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How to do it: select a group of individuals who do not yet have the outcome of interest. Group study participants by exposure without changing it. Measure influence variables (nutrient intake, carcinogen exposure, etc). Ensure that participants are not lost to follow-up. Compare outcome between groups.
Example: dietary habits have been measured in a large group of female professionals. Their risk of breast cancer was monitored for seven years. Women with lower fat intakes had a lower risk of breast cancer than those with high intake. |
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What are the Advantages/Disadvantages of Cohort Studies?
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• Advantages
o Dietary habits and other relevant exposure can be assessed more reliably before the disease develops. By selecting participants before the disease develops, selection bias is minimized. Answers for new questions may be obtained by analyzing the database of completed studies; if biological samples are available, additional measurements may become available. Many different hypotheses can be addressed because a number of different diseases will naturally develop in a cohort • Disadvantages o The number of people with very low and very high intakes may be too small. This is the most expensive and time-consuming type of epidemiological study • What you need to know o Prospective cohort studies are useful to test broad hypotheses, such as habitual consumption of major food groups. Because the disease has not developed yet, selection and recall bias are reduced. When the intake of whole foods is measured, special care must be taken before conclusions are drawn about the effects of individual nutrients. The effective anticarcinogen may be another compound for which intake data have not been calculated |
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How does one perform a Controlled Trial?
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How to do it: select a group of individuals who do not yet have the outcome of interest. Randomly assign different individuals to two or more groups. Compare the outcome between groups
Example: cancer-free elderly smokers in Finland were randomized to receive either 20mg synthetic beta-carotene or a placebo for seven years. The rate of newly detected lung cancer was 17% higher for users of the beta-carotene supplement than for people receiving placebo. |
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What are some Advantage/Disadvantage of Controlled Trials?
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• Advantages
o The effectiveness of a particular intervention in humans can only be tested in this way • Disadvantages o Extremely expensive and time-consuming. Only very specific hypotheses can be tested. Many studies become obsolete before they are even completed, because new evidence has been found in the years after inception. Because of the long duration, a significant percentage of participants may not be able or willing to continue to the end. Usually participation rates of 75% or better indicate reliability of the results • What you need to know o The focus of controlled studies is deliberately narrow. Your own question may differ significantly, because your patients have pre-existing disease, are older, or have different exposures to carcinogens. Low participation rate makes it difficult to prove that the intervention is effective. |
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What is Cachexia
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Cachexia, the clinical wasting syndrome characterized by weakness and progressive loss of body weight, muscle, and fat, can occur even in the presence of adequate nutrition
Tumor induced anorexia and increased energy expenditure promote weight loss Cytokines produced by the immune system and the tumor exert central and peripheral effects that lead to anorexia and the catabolism of body tissues Depression and adverse effects of therapy may also reduce the appetite |
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How does Weight loss affect ones nutritional Status?
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• Weight loss, a common but serious side effect of cancer, may impair functioning and worsen prognosis
• Although some tumors are more likely to be associated with weight loss than others, no correlation exists between the size of the tumor and the degree of weight loss. Very small tumors can sometimes cause significant weight loss due to abnormal cytokine or hormone release • When diagnosed, many cancer patients have experienced significant weight loss (e.g. about 60% of lung cancer patients and approximately 80% of patients with upper GI cancers) • Weight loss greater than 10% of usual body weight often results in weakness, lassitude, and depression • Cancer patients often have difficulty maintaining an adequate nutritional status as a result of o The disease itself (obstruction, altered metabolism) o Side effects of drug therapy (nausea, pain, inflammation, difficulty swallowing, food aversions, changes in taste) o Psychological or social reasons (depression, isolation) • Feeding the cancer patient does not just feed the tumor. Maintaining an adequate nutritional status can improve the quality of life and response to treatment. |
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What is Nutritional Support?
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• Nutritional support forms an integral part of the care of patients with potentially curable tumors. Well-nourished cancer patients are likely to tolerate their treatments and any complications better than malnourished patients
• Even if nutritional support does not prolong life, it offers may benefits, including: o Improved psychological well-being o Increased comfort o Increased mobility o Decreased complication rates • Cancer patients often experience changes in taste and may need to try different foods or formulas. They may also require a diet with higher caloric and protein density. Consultation with a dietitian for specific dietary recommendations is helpful and appropriate • Nutritional supplements are helpful for patients with oral or esophageal mucositis, or for those who have difficulty getting enough calories • Some patients may require short term TPN or tube feeding (e.g. after a bone marrow transplant) • The bottom line: optimal nutritional support improves survival or reduces suffering |
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How does one Manage the Side Effects of Cancer Treatment?
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• Radiation and chemotherapy produce many side effects that prevent patients from eating normally. Cancer therapy also accelerates the loss of nutrients, such as zinc. Zinc deficiency is one cause of diminished or altered taste sensation
• In general patients should o Eat slowly o Consume small, frequent meals o Receive appropriate vitamin and mineral supplementation Symptom Foods to Encourage Foods to Avoid Altered taste Tart foods to overcome bitter, metallic taste Constipation High-fiber foods Cheese, bananas Decreased appetite High protein, high calorie, nutrient dense foods Diarrhea High protein, high calorie, nutrient dense foods Dairy and high fiber foods Difficulty chewing or swallowing Soft or pureed foods; liquid supplements Hard, sharp foods Fatigue High protein, high carbohydrate foods Infection High protein foods Raw fruits and vegetables Mouth lesions Soft, high protein foods; liquid supplements Hard, sharp foods Nausea Bland or salty foods served cold or unheated Sugary, greasy, smelly foods |
