Chapter 7: Etiologic Factors in Neoplastic Disease Flashcards
What are the 5 broad categories of causes of cancer?
1) Viruses
2) Gene and chromosome abnormalities
3) Failure of immunological defense
4) Heredity
5) Chemical carcinogens
Which virus causes some types of leukemias and lymphomas?
Human T cell leukemia-lymphoma virus (HTLV-1)
Which virus causes Kaposi’s sarcoma?
Human herpesvirus 8 (HHV-8) (occurs in AIDS patients)
Which strains of the papilloma virus predispose one to cervical carcinoma and squamous carcinomas of the mouth, throat, larynx, and skin not exposed to sunlight?
HPV 16 or 18
Warts caused by HPV
genital condylomas
Which viruses predispose one to primary liver carcinoma?
Chronic viral hepatitis B or C
What virus appears to predispose one to nasopharyngeal carcinomas and some lymphomas?
Epstein Barr virus
Mutations or derangements of what three types of genes are associated with loss of growth control and tumor formation?
1) Proto-oncogenes
2) Tumor suppressor genes
3) DNA repair genes
What are three means by which a proto-oncogene can become an oncogene?
1) Mutation
2) Amplification
3) Translocation
Abnormally functioning gene that stimulates cell growth excessively, leading to unrestricted cell proliferation
Oncogene
How many mutations do you need to create an oncogene?
One (only one of the chromosomal pairs has to be mutated; gain of function mutation)
Normal genes that function to suppress cell proliferation/mitosis, and prevent
replication of cells with damaged DNA (act at cell cycle checkpoints)
Tumor suppressors
How many mutations do you need to deactivate a tumor suppressor?
2 (they exist in pairs on homologous chromosomes, so both genes must cease to function before the cell malfunctions)
What is the most common genetic defect in human cancer?
p53
What percentage of human cancers have a defective p53 tumor suppressor?
Half
The guardian of the genome
p53
How does p53 function in a normal cell?
Prevents cell cycle progression of DNA damaged cells which allows time for DNA repair or promotes their apoptosis if they are sufficiently damaged.
What is the result of loss of p53?
1) Continued growth of damaged cells
2) Reduced chemotherapy effectiveness
3) Permits angiogenesis
What are the 3 genes most frequently mutated in cancer
1) p53 (TS)
2) Myc (onc)
3) Ras (onc)
What was the first human oncogene discovered?
Ras
Mutations in this important tumor suppressor are associated with drug resistance and treatment failure.
p53
Mutations in these 2 oncogenes are associated with increased cell proliferation.
Myc and Ras
What percentage of human cancers have a mutated Myc?
40%
What percentage of all cancers have a mutated Ras?
20-30%
Which types of genes regulate normal processes that monitor and repair any errors in DNA duplication during cell division?
DNA repair genes
What is the result of failure of DNA repair genes to function?
Increased likelihood of mutations, including proto-oncogenes and tumor suppressors, leading to unrestrained cell growth.
How many of the genes of the chromosomal pair must become non-functional for DNA repair function to be lost?
Both genes
What is the result of inactivated DNA repair genes?
Increased mutation rate
These genes inhibit cell proliferation
Tumor suppressor genes
These genes correct errors in DNA duplication
DNA repair genes
What is the name of the reciprocal translocation between chromosomes 9 and 22 that forms a composite bcr/abl gene with overactive Tyr kinase activity that affects cell growth
Philadelphia chromosome
