Exam 3: Neoplasia II Flashcards
What are the most common cancers of adult males? Adult females? (the “big 4”)
i. Prostate/Breasts ii. Lung & bronchus iii. Colon and Rectum iv. Urinary bladder
What are the most common causes of cancer death in adult males? Adult Females?
Most common adult cancers are epithelial. 1) Lung (30%) 2) Prostate/Breast 3) Colon/rectum 4) Pancreas Cancer rates in obese individuals is more than 50% higher in both men and women compared to non-obese individuals.
What is the peak age for cancer in adults?
AGE 50-85
What cancers are associated with alcohol abuse?
Increased risk of head and neck/ upper aerodigestive system cancers Oropharynx, Larynx, Esophagus
What cancers are associated with tobacco smoke?
Head and neck/ upper aerodigesEve tract Lip, mouth/oropharynx, larynx, lungs, esophagus Lungs:(90% of lung cancer deaths) Pancreat cancer (specifically shown to be caused by tobacco use) Urinary tract: renal cell carcinoma Carcinoma of the uterine cervix
What cancers are associated with UV radiation?
Skin cancers Squamous cell carcinoma, basal cell carcinoma, malignant melanoma Most at risk individuals: fair skin, repeated sunburn, those unable to tan Caused by UV-B and UV-A wavelength: local immune suppression and DNA damage
Know the occupational carcinogens from Table 7-3 reproduced in lecture notes:
arsenic: lung/skin/hemangiosarcoma asbestos: lung(mesothe)/GI benzene: leukemia/Hodgkin lymphoma: Barylium: lung Cadmium: prostate Chromium: lung Nickle: nose/lung Radon: lung Vinyl Chloride (plastics): angiosarcoma/liver
23) How is inflammation associated with cancer? Review Table 7-5
Cancer develops at sites of chronic inflammation such as→ ulcerative colitis, gastritis Inflammation may predispose systemically to an increased risk of other cancers due to: 1) Cytokine stimulation of new cell growth→ increase pool of stem cells 2) Generation of free radicals→ ROS damages DNA
24) What is sporadic cancer? What is familial cancer? What is the frequency of familial cancer related to single gene germ line mutations?
Sporadic cancer→ due to new mutations Familial cancer→ inherited predisposition (usually enzyme or receptor polymorphisms→ ADH, alcoholdehydrogenase) ***Both environmental influences and genetics work together to cause cancer*** Frequency of familial cancer→ < 10% Frequency of single gene germ line mutations→
What characteristics suggest a familial cancer?
Characteristics of familial caner: 1) Clustering within families (2 or more relatives in direct line) 2) Occur at younger age, but most cancers peak at >50 years 3) Multiple or bilateral cancers 4) Autosomal dominant with variable penetrance; mulifactorial ⇒ Common familial cancers include: breast, colon, ovary, brain and malignant melanoma Other characteristics include: polymorphism of p450 enzymes, polymorphisms for receptors
Know Knudson’s two hit hypothesis and how it relates to understanding familial cancer
Two mutations “hits” of Rb gene required to produce retinoblastoma Patient with familial retinoblastoma inherits 1 defective gene copy in all cells = 1st hit 2nd copy lost by somatic mutation= 2nd hit 2 hits→ malignant transformation 2 types of retinoblastoma: 1) Sporadic (most common)→ both hits occur as independent, somatic mutations 2) Familial Rb mutations (sporadic or familial) all have the same presentation, pathology, metastatic pattern The difference is the frequency.
Describe each of the three inherited cancer syndromes with marker phenotypes
1) Familial adenomatous polyposis of the colon (FAP) Develop 100 or more polyps of the colon in late adolescence or early adulthood with 100% risk of malignant transformation in one or more polyps by age 50 yrs. Mutation: APC gene mutation 2) Multiple endocrine neoplasia (MEN syndrome) 3 distinct patterns of multiple tumors of: parathyroid, pituitary glands, c-cells of thyroid and pancreatic islet cells 3) Neurofibromatosis (**most common of the 3**) Multiple benign neurofibromas, each at risk for transformation→ neurofibrosarcoma Café au lait spots; Lisch nodules Mutation: defect of tumor suppressor gene (inherited)
List the autosomal recessive tumor cancers of DNA repair. What is xeroderma pigmentosa, its cause and consequences?
1) Xeroderma pigmentosa→ disordered nucleotide excision repair which results in extreme photosensitivity to UV light Results in: 2000x increased risk of developing skin cancer (squamous and basal cell carcinomas and malignant melanoma) Skin cancer occurs in childhood 2) Ataxia telangiectasia→ ATM (ataxia telangiectasia) gene is mutated and results in chromosome fragility ATM gene binds to damaged DNA and phosphorylates TP53. Heterozygous state of ATM is common (1% of population) and these individuals have an increased predisposition for cancer. Results in: cerebellar ataxia, oculocutaneous telangiectasis (dialated blood vessels), IgA deficiency (recurrent sinopulmonary infection); sensitivity to ionizing radiation (develop leukemia, lymphoma with exposure to radiation) 3) Fanconi’s anemia→ Results in: physical abnormalities, pancytopenia (reduction in blood cell types →RBC’s, platelets, and neutrophils), chromosome fragility, risk for leukemia, squamous cell carcinoma and hepatoma 4) Bloom syndrome→ homozygous for BLM gene mutations. Heterozygous BLM gene mutations predispose individuals to an increased risk of colorectal carcinoma. Results in: cutaneous manifestations, immunodeficiency, sensitivity to UV radiation, increased risk for leukemia/lymphoma.
Describe the steps in chemical carcinogenesis. What are characteristics of chemicals involved in each step?
1) Initiation: insufficient alone for tumor formation; rapid, irreversible effect (permanent DNA damage) Outcomes of exposure to initiators: a) Cell death b) DNA repair→ return to normal c) Permanent DNA damage→ must undergo one successful cell cycle to make permanent DNA mutation Types of Initiators 1) Direct acting: require no chemical transformation, highly reactive electrophilic (attach to DNA forming adducts) 2) Indirect acting: pro-carcinogens metabolized to ultimate carcinogens by P-450 dependent enzymes 2) Promotion: effects reversible; promoters are not tumorigenic by themselves; induce tumors in initiated (mutated) cells (initiated cells respond differently than normal cells Promoters include: hormones, phenols, drugs Effects of promoters: Induce sustained cell proliferation (↑risk of additional mutations)
What substances are direct acting chemical carcinogens?
Direct acting chemical carcinogens do not require metabolic conversion, and they are generally weak in action. 2 Classes: 1) Alkylating agents: cancer chemotherapy drugs, cyclophosphamide, chlorambucil → some patients using these develop secondary cancer 2) Acylating agents
List specific named chemicals involved in carcinogenesis. Know the cancers with which they are associated.
