Epi and carcinogenesis Flashcards
4 most common CA
lung, breast, colon, prostate
how many canadians will get CA and how many will die of itq
get - 40%
die - 25%
what is most deadly common CA
lung
2 things that CA incidence patterns reflects
- presence of env. factors
2. primary prevention
2 types of primary prevention
- lifestyle mod
2. screening
3 things that CA mortality rates reflect
- effect of screening
- natural Hx of Ca
- treatments
how is race important (2)
- may define risk groups
2. may reflect presence of polymorphisms in a pop. that increase thier susceptibilty
3 genetic influnces on CA
- genomic instability - natural mutations
- inherited mutation
- acquired mutation
4 ways cells try to prevent accumulation of mutations
- continuous shedding of certain cells - epithelial stress
- defenses against genotoxic injury
- DNA damage checkpoints in cell cycle
- cellular sensence
what % of CA have a notable genetic component
5-10%
2 types of inhertiance patterns
- specific recognized defect
2. general familial predisposition
2 types of specific recognized defects
- inherited CA syndromes
2. defective DNA repair syndromes
what is mech. of inherited CA syndrome
- germline mutation of in one allele of critical gene (usually tumor supressor)
- mutation of second allele in somatic cells
- dysregulation of cell growth and prolif.
who do inherited syndromes present
usually a specific phenotype
- except Li- fraumeni syndrome
what is defective DNA- repair syndrome
usually rare and via defects in ability to repair DNA causing subsequent mutations
**how to tell if mutation is due to inherited mutations
if sporadic, the mutations will only be in tumour cells
characterisitcs of familial predisp. to CA
higher freq., but no pattern
- early age of onset
- multiple or bilateral tumors
- no specific marker or transmission pattern
what are vast majorty of mutations in CA
aquired via env.
some env. influences
diet, smoking, alcohol, chemiscals, radiation
what are 2 types of carcinogens
direct - no metabolic activation needed
indirect
2 steps in chemical carcinogens
- initiation - exposure causes mutation
- not sufficient to cause cancer - promotion - causes damaged cells to prolif
what are 2 types of radiation
- UV - due to formations of crosslinks in DNA
2. ionizing - often leukemias, thyroid, breast colon
3 classes of microbial carcinogens and examples
- RNA viruses
- HTLV-1 - DNA viruses
- HPV
- HBV
- EBV
- HHV-8 - bacteria
- h. pylori
what is cancer and cause of HTLV-1
CA - T-cell leukemia - 3-5%
cause - tropism for CD4 - viral integration into genome
what is cancer and cause of HPV
CA - cervical
cause - 16 and 18 - viral integration causing genomic instability
what is cancer and cause of EBV
CA - lymphoma
cause -
what is cancer and cause of HBV
CA - 70-80% hepatocellular carcinoma
cause - immune mediated chronic inflammation
what is cancer (2) and cause of pyloori
CA - 1. gastric adenocarcinoma 2. gastric lymphoma
cause - 1. CagA gene , 2. gen. reactive T cells - polyclonal B cell proliferation
how is age related
generally older due to accumulation of mutations and decline in immune competence
common CA in children
leukemias and blastomas
3 other predisposing factors
- conditions that result in cell prolif (hyper and metaplasias)
- chronic inflammatory disorders (UC, h pyloir, hepatitis)
- dysplastic lesions - not ALL will progress
