Cancer Flashcards
Neoplasm
“new growth” or “tumor”
An uncontrolled growth of new cells.
May be benign or malignant
Benign
A neoplasm not capable of metastiasizing
usually not capable of causing death
“bulk effect” may compress tissues around it
Malignant
“Cancer”
Neoplasm capable of metastasizing
Capable of causing death- various ways it can do this.
Men and women risk of cancer
Men 1:2
Women 1:3
How can some cancer types be preventable?
30% of cancer death caused by tobacco use
30% related to obesity, physical inactivity, and poor nutrition.
Preventable causes of cancer
HPV vaccine
HBP vaccine
HIV safe practices, PREP prophylactic med.
Heliobacter pylori (can treat with antibiotics)
Skin cancer
Of cancers that affect the eye:
Only ____% of cancers are primary to the eye
___ of cancers metazoic to the eye
5-10% primary
90-95% metastatic to the eye.
Where do cancer typically spread to in the eye?
Uvea. Highly vascularized.
Most common cancers that spread to the eye
Breast and lung cancer
Transofmration
Normal cells become cancer cells. This is a long process.
How can cancer cells gain autonomy through mutation?
They gain independence from normal cellular controls.
They become anchorage independent (do not need to be anchored in order to divide)
Immortal (telomerase activity)
Evade/avoid apoptosis (telomerase activity)
Angiogenic
Self-stimulating
Insensitive to anti-growth signals
Invasive
Loss of telomeres in a normal cell=
Apoptosis
What does it mean that cancer cells are anchorage independent?
They do not exhibit contact inhibition and continue to divide, piling up on top of each other. They can proliferate suspended in a soft agar- normal cells cannot and need to be anchored.
How can chronic inflammation lead to cancer?
Creates a hyper proliferative environment via cytokines and free radicals. Cytokines signal for cell proliferation and angiogenesis. Free radicals cause DNA damage and can lead to mutation.
Tumor is a wound that
Fails to heal. Cancer cells avoid/evade immune system.
Cancer causes: 3 mechanisms
- Chronic inflammation without infection
- Chronic infection with inflammation
- Genetic mutations (inherited or environmental)
External causes of cancer
Toxins (workplace, cigarette smoke) causes DNA damage or inflammation.
Infections (bacteria, virus, fungus, parasite) cause DNA damage and/or chronic inflammation.
Radiation causes DNA damage
Internal causes of cancer
Hormonal imbalance- breast, ovarian, and colon cancer (maybe due to insulin resistance in obesity)
Autoimmune diseases- chronic inflammation
Metabolic disorders: Metabolic byproducts may have toxic effects.
Mutagens
Chemical or physical agent that causes a change in the DNA of a cell.
Carcinogen
A type of mutagen that contributes to the development of cancer. Changes DNA or metabolic processes.
Causes non-lethal genetic damage
Two types: Initator, promotor
Two types of carcinogens
Initiator: Causes genetic damage
Promotor: promotes tumor growth
Factors that might be carcinogenic
Insecticides Nitrates Cisplatin Haridresser inhalants Very hot beverages
Factors that are definitely carcinogenic
Plutonium (radioactive) Benzene (oxidation) HPV Alcoholic beverages Tobacco smoke Tanning beds
How can viruses cause cancer?
Inserting genetic material into infected cells.
Initiating a chronic inflammatory response.
Viruses associated with cancers
Hepatitis B and C Epstein Barr Herpes virus Human papilloma virus 100% causes cervical cancer Lymphoma virus
How can bacteria cause cancer?
Chronic infection= chronic inflammatory response = cancer
More likely with high concentration of bacteria
Helicobacter pylori associated with peptic ulcer disease, stomach carcinoma, and MALT lymphomas.
Cancer tends to involve multiple mutations
Mutation inactivates suppressor gene
Cells proliferate
Mutations inactivate DNA repair genes
Proto-oncogenes mutate to oncogenes
Proto-oncogenes
Code for proteins that regulate cell growth and proliferation.
Normal and necessary
Capable of becoming an oncogene with one mutation.
Oncogene
Can cause a cell to become a cancer cell.
Come from mutated proto-oncogene.
Growth and proliferation are no longer regulated.
Over-active growth signals. More receptors = more activity.
Tumor suppressor genes
Act like a break pedal. Slow down cell proliferation or induce apoptosis when cell damage is present. Same as anti-oncogenes.
Anti-oncogenes
Tumor suppressor genes. Act like a brake pedal.
What happens if there is a mutation in a tumor suppressor gene?
Mutation allows for unregulated growth. Both copies must be inactivated for progression of cancer
How many copies of the tumor suppressor gene must be inactivated for progression of cancer?
2
p53 (a tumor supressor gene)
P53 is activated if there is DNA damage. It will be made into a protein that can stall division until the DNA is fixed. High levels of P53 protein in the cell will initiate apoptosis.
Most common tumor suppressor gene defect
P53.
Greater than 1/2 of all types of tumors lack functional p53.
What is the goal of chemotherapy/radiation?
Will hopefully cause DNA damage, activating p53 to be made.
This will only work if there is a functioning P53 allele in the cell. Cell with 2 mutated alleles will not respond to chemo.
Point mutation
Changes in 1 base pair. Ex: Sickle cell anemia
Can be mutated or inherited
Gene amplification mutation
Duplication of a small piece of chromosome over and over. Can result in an increased expression of an oncogene. Greater likelihood it could mutate into protoncogene.
Chromosome translocation in somatic cell mutation
Piece of one chromosome is transferred to another. Leads to excess production of abnormal protein or novel protein that may have new role.
Ex: Chronic myeloid leukemia and philadelphia chr (9 +22 translocation)
What happens if there a mutation to a caretaker gene?
Loss of these genes lead to increased mutation.
Normal role is to help with gene repair.
Chromosome instability (increased in malignant cells after continuous replication) occurs during mitosis and can lead to:
Chromosome loss
Loss of heterozygosity
Chromosome amplification (duplication of small piece of Chr over and over)
How could an epigenetic mutation lead to cancer?
Abnormal silencing of tumor suppressor genes could lead to cancer. By methylation or histone modification.
Or loss of silencing for oncogenes. (Taking foot off break -tumor suppressor gene, and putting it on the gas- oncogene)
Hereditary cancers are largely associated with
Tumor suppressor genes and rarely associated with oncogenes.
Usually heterozygous initially, then at risk for loss of heterozygosity.
How many cases of retinoblastoma are inherited
1/2 due to mutated/deleted Rb1 gene that should suppress cell growth.
What does RB1 code for in retinoblastoma
Proteins, pRB, that suppress growth. Regulates cell cycle.
Clinical signs of retinoblastoma
Leukocoria
Strabismus
Loss of vision
Is retinoblastoma unilateral or bilateral
75% are unilateral.
All bilateral cases are inherited.
Hereditary of retinoblastoma
Autosomal dominant with incomplete penetrance
How can you lose heterozygosity
Child must be born heterozygous for the allele- one normal and one mutant. Occurs when eyes are developing, during on-going cell division.
- Messegregation
- Mitotic recombination
