L7 Neoplasia II Flashcards
Cancer is the ___ leading cause of death in the U.S.
Second
What are the 7 major variables leading to cancer?
- Geography
- Environmental
- Age
- Race
- Acquired predisposing conditions
- Genetic predisposition
- Genetic/inherited factors
Geographic variation in incidence of cancer is though to stem from differences in ___.
Exposure (to environmental carcinogens)
What are agents that damage DNA increasing risk for cancer?
Carcinogens
What are some environmental risk factors for cancer?
- Tobacco
- Alcohol
- Obesity
- Occupational exposures
- Sunlight
- Radiation
- Sexual exposures
Frequency of cancer increases with age - why?
Rising accumulation of somatic mutations and decline in immune competence.
True or false - most cancers are familial.
False - most are sporadic.
What are the three general patterns of inheritance for cancer?
- Autosomal dominant cancer syndromes
- Autosomal recessive syndromes of defective DNA repair
- Familial cancers of uncertain inheritance
What are two examples of autosomal dominant cancer syndromes?
- Familial adenomatous polyps of colon
2. Familial retinoblastoma
What generally characterizes autosomal recessive syndromes?
Chromosomal or DNA instability
What is an example of an autosomal recessive syndrome?
Xeroderma pigmentosum
What are two examples of acquired predisposing conditions?
- Chronic inflammation
2. Chronic tissue injury (smoking)
Cancer is a ___ disorder caused by ___.
Genetic; DNA mutations
What are the 4 classes of normal regulatory genes that are targets of cell damage?
- Proto-oncogenes
- Tumor suppressor genes
- Genes that regulate apoptosis
- Genes involved in DNA repair
Describe the promotion of proliferation by oncogenes.
- Growth factors and cytokines affect proto-oncogenes.
- Proto-oncogenes code for cyclins D and E
- Cyclins D and E activate CDK 2, 4, 6
- CDK 2, 4, 6 phosphorylate Rb, which in its unphosphorylated form binds E2F, blocking transcription.
- Phosphorylated Rb releases E2F, which binds to DNA and advances the cell cycle
Describe the control of proliferation by oncogenes.
- DNA damage, oncogenic activation, and hypoxia stimulate p53.
- p53 stimulates CDK inhibitors
- CDK inhibitors inhibit CDK and prevent the phosphorylation of Rb
What are normal cellular genes whose products promote cell proliferation?
Proto-oncogenes
What are mutant or over-expressed versions of normal proto-oncogenes?
Oncogenes
Name the gene product and associated tumor of the oncogene: ABL
Tyrosine kinase
Chronic myelogenous leukemia
Name the gene product and associated tumor of the oncogene: C-MYC
Transcription factor
Burkitt Lymphoma