B2.078 Cancer Biology Flashcards
how does chromic inflammation affect cancer risk?
increases risk due to increasing cell proliferation and increased possibility for damage (ROS)
what are proliferative precursor lesions?
metaplasia- sustained injury
hyperplasia- hormonal stimulation
how does immunodeficiency affect cancer risk?
increases risk due to inability to fight off cancer cells without immuno-surveillance mechanisms
what type of inheritance is exhibited in familial cancer?
polygenic or multifactorial
can’t pinpoint specific genes but appears to run in families
what are some clinical features of hereditary cancer?
multiple affected relatives early age of cancer onset bilaterally affected organs multiple primary cancers in same individual autosomal dominant pattern
what are the differences in risk associated with hereditary cancer associated w tumor suppressor genes vs, DNA repair genes?
both risks elevated
tumor suppressor mutation = virtually 100% likelihood of getting cancer
DNA repair mutation = highly likely, but may develop later or possibly not at all if DNA damage never occurs in a cancer specific gene
how many retinoblastoma patients have unilateral vs bilateral tumors?
70% uni
30 % bi
what percentage of retinoblastomas are hereditary?
40%
all bilateral are hereditary, but not all hereditary forms result in bilateral tumors
how does heritable retinoblastoma affect risk of developing other cancers?
400 fold increase
what tumor suppressor gene is associated with Li-Fraumeni Syndrome?
TP53
what are some tumors that often result from Li-Fraumeni Syndrome?
breast carcinoma soft tissue sarcoma brain tumors osteosarcoma leukemia
what gene is associated with familial adenomatous polyposis (FAP)?
APC
how is FAP recognizable?
100s-1000s of colonic polyps in teenage years
what is the best treatment for FAP?
removal of the colon early in life
what is HNPCC?
hereditary non-polyposis colorectal cancer
Lynch Syndrome
differentiate between HNPCC and FAP
HNPCC: early onset, but later than FAP germline mutation in mismatch repair genes 5% of colon cancer recognized by DNA slips in microsatellites alerting to poor repair mechanisms (MSH) FAP: very early onset germline mutation in APC gene 1% of all colon cancer recognized by polyps
what percentage of breast cancers are inherited?
5-10%
how does inheriting a BRCA gene mutation affect lifetime risk of cancer?
40-85% increase in breast cancer risk
BRCA1 55% and BRCA2 25% ovarian cancer risk
what are the steps of chemical carcinogenesis?
initiation (permanent DNA damage)
promotion (proliferation stimulation)
what are direct acting carcinogens?
alkylating/acylating agents
usually weak
used in chemotherapy
what are indirect acting carcinogens?
aromatic hydrocarbons, dyes, toxins
metabolic conversion required (cp450)
strong carcinogens
what are the 2 types of radiation carcinogenesis?
UVB exposure and ionizing radiation
what is the mechanism by which UVB exposure causes cancer?
formation of pyrimidine dimers
normally repaired by nucleotide excision repair (XP pathway), but can be overwhelmed or dysfunctional
what is the mechanism by which ionizing radiation causes cancer?
chromosomal breakage, translocations, point mutations
what are some examples of microbial carcinogens?
retrovirus- HTLV-1
DNA virus- HPV, EBV, HBV, HHV8
bacteria- helicobacter pylori
how do microbial carcinogens cause cancer?
viral integration into genome
direct activation/proliferation by interaction w tumor suppressor genes
increased genomic instability
immunological damage with resultant proliferation of lymphocytes/epithelial cells
how do HPV E6 and E7 inactivate Rb protein?
inhibits RB-E2F complex increases CDK4/cyclin D1 inhibits p21 inhibits p53 increases telomerase
what disease is associated with EBV?
Burkett lymphoma
set up uncontrolled B-cell proliferation resulting in mutations
(increased C-MYC expression)
which oncogenes are affected by translocations?
c-MYC (burkitt lymphoma) -t(8:14) BCL2 (follicular lymphoma) BCR/ABL (chromic myeloid leukemia) -t(9:22)
which tumor suppressor gene is affected by deletions?
Rb
which oncogenes are affected by gene amplification?
N-MYC (neuroblastoma)
HER-2/neu (breast cancer)
which oncogenes are affected by point mutations?
RAS (many cancers)
what are some epigenetic changes that can affect dysregulation of cancer genes?
local hypermethylation, global changes in methylation, changes in histones
what is a growth fraction?
proportion of cells in a cell cycle that are actively dividing
what are the 3 routes of cancer spreading?
hematogenous
lymphatic
body cavity seeding
what are some local effects of cancer related to direct tumor growth?
mass bleeding compression/obstruction rupture/torsion vascular compromise necrosis functional manifestations
what are the two major systemic effects of cancers?
cachexia - profound weakness, anorexia, anemia
paraneoplastic syndrome- clinical findings not directly explained by anatomic location or functional output of the cancer
what are some features of cachexia?
equal loss of fat and lean muscle
elevated basal metabolic rate
evidence of systemic inflammation
what are characteristics of a good screening test?
high sensitivity variable specificity high NPV variable PPV variables dependent on prevalence
what are some types of cancer screening tests?
clinical exam and procedures radiological imaging biochemical measurement cytologic exam histologic exam nucleic acid testing for markers
