Carcinogenesis Flashcards
Carcinogenesis
Transformation of normal cells to neoplastic cells by causing permanent genetic alterations.
Carcinogen
An environmental agent participating in the causation of tumours.
Can be carcinogenic (cancer causing) these are also mutagenic or oncogenic (tumours causing).
Multistep carcinogenesis hypothesis
More than one carcinogen is necessary for the complete neoplastic transformation of a cell.
Hit-and-run situation
Specific causative agent is not usually found in the eventual tumour.
Why is it difficult to identify a single causative factor of CA?
Long time interval between exposure to a carcinogen and the appearance of signs and symptoms = latent interval.
Carcinogens can be identified from
Epidemiological studies
Assessment of occupational risks
Direct accidental exposure
Carcinogenic effects in laboratory animals
Transforming effects on cell cultures
Mutagenicity testing in bacteria
Carcinoma of the cervix is associated with what genotypes of HPV?
16 & 18.
Since carcinogens are not united by any common physical or chemical properties, what needs to be done to check their safety…
Testing in non-human system.
Bacterial cultures for mutagenicity testing (Ames test).
Cell and tissue cultures in which growth-transforming effects are sought.
Laboratory animals in which the incidence of tumours is monitored.
What are the main classes of carcinogenic agents?
Chemicals
Viruses
Ionising radiation
Non-ionising radiation
Exogenous hormones
Bacteria/fungi/parasites
Miscellaneous agents
Chemical carcinogens
Some directly damages
Some requires metabolic conversion (procarcinogen) -> ultimate carcinogen.
Oncogenic viruses
Oncogenic DNA viral genome - directly incorporated into host DNA.
Oncogenic RNA viral genome - reverse transcriptase - then incorporated.
HHV8
Kaposi sarcoma
EBV
Burkitt lymphoma, nasopharyngeal carcinoma
HBV
Hepatocellular carcinoma
HPV
Squamous cell carcinomas of the cervix, penis, anus, head and neck
MCV (Merkel cell polyomavirus)
Merkel cell carcinoma
HTLV-1 Human T-lymphotrophic virus
Adult T-cell leukaemia
HCV
Hepatocellular carcinoma
Why is UVC not causing CA?
It is reflected by the atmosphere so never reaches the surface.
Which type of UV light is a bigger causal factor?
UVB>UVA
Host factors in carcinogenes
Race
Diet
Constitutional factors
Premalignant lesions and conditions
Transplacental exposure
Multiple endocrine neoplasia (MEN) syndromes
Endocrine tumours.
Autosomal dominant MEN1 gene on Cr. 11 and RET gene on Cr. 10
Xeroderma pigmentosum
Skin cancers.
Autosomal recessive XP genes.
Familial adenomatous polyposis coli (FAP)
Colorectal adenomas and adenocarcinomas.
Autosomal dominant; APC gene on Cr. 5
Hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome
Colorectal carcinoma and other tumours (endometrium, ovary…)
MLH1 on Cr. 3
MSH2 on Cr. 2
Autosomal dominant
von Hippel-Lindau syndrome
Renal cell carcinoma, phaeochromocytoma…
Autosomal dominant VHL gene on Cr 3.
Li-Fraumeni syndrome
Breast carcinoma
Autosomal dominant mutant p53 on Cr 17
Retinoblastoma syndrome
Retinoblastoma
Autosomal dominant RB1 gene on Cr 13
Familial brast carcinoma
Breast carcinoma, ovarian carcinoma
Autosomal dominant.
BRCA1 on Cr 17
BRCA2 on Cr 13
Fanconi anaemia (FA)
Leukaemia
Autosomal recessive FANC gene
