1. Cancer Rachel Cox, Sarah Kunz, Asia Camara, and KayliCummings

2. Cancer • Disease involving abnormal division and reproduction of the cells that can spread throughout the body • 100 distinct types of cancer • Cost is $48 billion annually

3. Cancer • 13.7 million Americans with a history of cancer were alive in January 1, 2012 • Lifetime risk= probability that an individual will develop or die from cancer • Men= slightly less than a 1 in 2 lifetime risk of developing cancer • Women= slightly more than 1 in 3. • The second most common cause of death in the US • 1 of every 4 deaths • 5-year survival rate • All cancers diagnosed between 2001-2007: 67% • All cancers diagnosed between 1975-1977- 49%

4. 1,660,290 new cases expected in 2013 *excluding in situ cancer or basal cell or squamous cell skin cancers 580,350 Americans expected to die from cancer in 2013

5. Etiology Including risk factors

6. External Risk Factors • Tobacco/ cigarette smoking • Alcohol • Alcoholism and malnutrition • Excess energy • Calorie restriction • BMI (gastric surgery) • Insulin Resistance (IGF-1) • Carbohydrate intake • Fats • Protein

7. External Risk Factors Continued • Infectious organisms • Hepatitis B, HPV, HIV, H. Pylori • Radiation/ UV rays • Limited fruit, vegetable, and fiber consumption • Chemicals/ Carcinogens • N-nitroso compounds (NOC) • Polycyclic aromatic hydrocarbons (PAH) • Bisphenol A (BP-A) • others

9. 77% of all cancers are diagnosed in people over 55 years old

10. Internal Risk Factors • Genetic damage • Inherited mutations (5%) • Hormones • Immune conditions • Mutations in metabolism • Most mutations occur during life

11. Gene Variants and Cancer • Detoxification system • Cytochrome P450 isozymes (CYPs) • Glutathione S-transferases (GSTs) • Superoxide dismutases (SODs) • Codes for proteins that dismantle reactive Oxygen species • Each if affected by Nutrition • Lots of research on this relationship

12. Cancer Incidence and Death Rates by Site, Race, and Ethnicity, US, 2005-2009*All sites per 100,000 Americans, age adjusted

13. Prevention 1/3 cancer deaths in the U.S. could be linked to diet and physical activity, including obesity

14. American Cancer Society Recommendations • Achieve and maintain a healthy weight throughout life • Avoid excess weight gain • Be as lean as possible without being underweight • Be physically active • Limit sedentary behavior • Adults: 150 minutes of moderate intensity or 75 minutes of vigorous intensity activity a week • Children and teens: 1 hour of moderate or vigorous intensity activity each day with vigorous activity 3 days a week

15. ACS Recommendations Cont. • Eat a healthy diet with an emphasis on plant foods • Choose foods and drinks to maintain healthy weight • Limit processed meat and red meat • Eat at least 2 ½ cups of vegetables and fruits a day • Choose whole grain products • Watch portion control

16. ACS Recommendations Cont. • Limit alcohol intake • 1 drink/day for women, 2 drinks/day for men • Community Action • Increase access to affordable and healthy foods • Provide safe, enjoyable, and accessible places for physical activity

17. Prevention • Antioxidants • Vitamins A,C,E, carotenoids, selenium, zinc • Protein/ fat source • Omega 3: Omega 6 ratio • Leaner cuts of red meat and smaller portions or other meat sources • Calcium and Vitamin D • Conflicting studies on calcium supplementation or increased dairy intake • Vitamin D possibly preventative from colorectal cancer • Vitamin D may increase risk for aggressive prostate cancer • High serum levels associated with lower risk of many cancers • Folate and Folic Acid • Soy and Phytoestrogens

18. Phytochemicals • Mechanisms: • Detoxification of enzymes • Inhibition of nitrosamine formation • Provision of substrate for formation of chemotherapy agents • Dilution and binding of carcinogens in GI tract • Alteration of hormone metabolism • Antioxidant effects

19. Polyphenols (Phytochemicals) • Carotenoids • Flavonoids • Isoflavones • Lignans • Organosulfides • Phenolic compounds • monoterpenes • Sources: • Fruits and vegetables • Nonstarchy vegetables- green and yellow • Grapes and berries- resveratrol • Tea and Coffee • Curry • Curcumin

20. Pathophysiology

21. Classification and Nomenclature • Carcinomas: malignant epithelial tumors • Adenocarcinoma: cancer tumor from ductal or glandular structures • Adenoma - benign tumor in similar location • Sarcomas: malignant connective tissue (non-epithelial) tumors • Lymphomas: cancers of lymphatic tissue • Leukemias: cancers of blood-forming cells

22. Benign vs. Malignant Tumors

23. Differentiation

24. Differentiation

25. Anaplasia = absence of differentiation

26. Carcinogenesis • Initiation • Transformation of cells in response to carcinogenic agents • May be years from initial damage to detectable cancer • Promotion • Neoplasm formed through failure of protective mechanisms • Progression • Tumor formation • Metastasis • Angiogenesis

27. Pathophysiology • Proto-oncogene: normal gene that codes for cellular growth • ras • Oncogene: mutated proto-oncogenes • Promote tumor growth • Change programmed cell death (apoptosis) • Tumor suppressor genes • Encode proteins that negatively regulate proliferation • p53

28. Initiation • Self-sufficiency in growth signals • Autocrine stimulation • increased growth factor receptors/ increased sensitivity of growth factor receptors • Mutation in caretaker genes • Insensitivity to antigrowth signals • Evading apoptosis • Limitless replicative potential • Sustained angiogenesis • Tissue invasion and metastasis • Over activity of Telomerase

29. Telomeres and Immortality • Telomeres: protective caps on each chromosome • Maintained by telomerase • Become smaller with each cell division • Cells can only divide a limited number of times • If telomerase over active, cell becomes immortal

30. Mutations • Point mutations • Changes in one or a few nucleotide base pairs • Chromosome translocation • Piece on one chromosome is transferred to another • Gene amplification • Duplication of a small piece of chromosome over and over • Can result in an increased expression of an oncogene

31. Carcinogenesis • Initiation • Transformation of cells in response to carcinogenic agents • May be years from initial damage to detectable cancer • Promotion • Neoplasm formed through failure of protective mechanisms • Progression • Tumor formation • Metastasis • Angiogenesis

32. Carcinogenesis • Initiation • Transformation of cells in response to carcinogenic agents • May be years from initial damage to detectable cancer • Promotion • Neoplasm formed through failure of protective mechanisms • Progression • Tumor formation • Metastasis • Angiogenesis

33. Mechanisms of Tumor Spread • Direct invasion of contiguous organs • Local spread • Metastasis to distant organs • Mechanical pressure • Lytic enzymes • Lymphatics and blood

34. Invasion! • Tumor cell attachment • Fibronectin • Laminin • Degradation or dissolution of the matrix • Enzymes (proteases, collagenases) • Locomotion into the matrix • Invadopodia

36. Staging of Cancer

37. Staging • Used to identify how much a cancer has spread throughout the body • Used as a strong predictor for survival • Used as a reference for the most effective treatment • Classified as Stage I, Stage II, Stage III, or Stage IV • Stage I being the least amt of disease and Stage IV being the most advanced.

38. Staging 1, 2, 3, 4 • Involves the size of the tumor, degree to which it has invaded, and the extent to which it has spread • Stage 1 • Cancer is confined to its organ of origin • Stage 2 • Locally invasive • Stage 3 • Regional structures • Stage 4 • Distant sites

39. Staging- TNM • Tumor-node-metastasis • T- stands for the size of the tumor • N- stands for the nodes or whether it has spread into the lymph nodes • M- stands for metastasis (whether the cancer has spread to distant organs)

40. Tumor

41. Nodes

42. Metastasis

43. Staging

44. Classification terms • In situ: Abnormal cells are present only in the layer of cells in which they developed. • Localized: Cancer is limited to the organ in which it began, without evidence of spread. • Regional: Cancer has spread beyond the primary site to nearby lymph nodes or organs and tissues. • Distant: Cancer has spread from the primary site to distant organs or distant lymph nodes. • Unknown: There is not enough information to determine the stage.

45. Grading 1, 2, 3, 4 *not to be confused with staging • Grading refers to the cancer cell differentiation • GX- Grade cannot be assessed (Undetermined grade) • G1- Well-differentiated (Low grade) • G2- Moderately differentiated (Intermediate grade) • G3- Poorly differentiated (High grade) • G4- Undifferentiated (High grade)

46. Diagnosing Cancer

47. Early Diagnosis C.A.U.T.I.O.N. • Change in bowel or bladder habits • A sore that does not heal • Unusual bleeding or discharge • Thickening or lumping in breast or elsewhere • Indigestion or difficulty in swallowing or chewing • Obvious change in a wart or mole • Nagging cough or hoarseness

48. Laboratory tests • Blood, urine, and other body fluids • Tumor markers- hormones, enzymes, genes, antigens, antibodies • Malignant tests • Histopathologic examinations, flow cytometry, immunohistochemistry and cytogenetics • Oxidative damage to lipids, proteins and DNA

49. Other signs Metastatic cancer General Signs • Anorexia • Fatigue • Weight loss • Fever • Sweating • Anemia • Pain • Enlarged lymph nodes or body organs • Cough with or without hemoptysis • Bone pain w/ or w/o fracture • Neurological symptoms

50. Cancer Images • CT Scan- (radiographic procedure which takes pictures at multiple angles)- evaluates for abnormalities in areas such as the head, chest, abdomen or pelvis • MRI Scan (radio waves and a magnet linked to a computer)- images produced show differences in normal and cancerous tissue. Mostly used in the brain, spinal cord and liver • PET Scan (follows radioactive glucose)- looks for ‘hot spots’ of high glycolysis in cancerous cells