Carcinogenesis Flashcards
What is carcinogenesis?
The transformation of normal cells to neoplastic cells though permanent genetic alterations or mutations
Which type tumour goes through carcinogenesis?
Malignant neoplasms
Which type of tumour goes through oncogenesis?
Benign and malignant tumours
What is a carcinogen?
Agents known or suspected to cause tumours
What is the difference between carcinogenic and oncogenic?
- Carcinogenic = cancer causing
- Oncogenic = tumour causing
What does mutagenic mean?
Acts on DNA
What occupational risk is bladder cancer seen in?
- Incidence in aniline dye and rubber industries
- β-naphthylamine
What occupational risk is scrotal cancer seen in?
- Incidence in chimney sweeps
- Polycyclic aromatic hydrocarbons
What is thorotrast?
- Colloidal suspension of thorium
- Irreversibly ingested by phagocytes
What is evidence of thyroid irradiation?
- 1986: Chernobyl nuclear reactor explodes
- Release of 125I and 131I into atmosphere
- 1990: ↑ incidence of thyroid cancer in Ukrainian children
Why may testing on animals and cell/tissue cultures not be comparable to humans?
- Animals / cultures may metabolise agents differently to humans
- Bacterial mutation may not = carcinogenecity
What are the classes of carcinogens?
- Chemical
- Viral
- Ionising and non-ionising radiation
- Hormones, parasites and mycotoxins
- Miscellaneous
Describe features of chemical carcinogens
- No common structural features
- Some act directly
- Most require metabolic conversion from pro-carcinogens to ultimate carcinogens
- Enzyme required may be ubiquitous (everywhere) or confined to certain organs
What are examples of chemical carcinogens?
Polycyclic aromatic hydrocarbons, aromatic amines, nitrosamines and alkylating agents
What cancer do polycyclic aromatic hydrocarbons cause and what can it be caused by?
Lung caner and skin cancer caused by smoking, mineral oils
What cancer do aromatic amines cause and what can it be caused by?
Bladder cancer found in rubber/dye workers
What cancer do nitrosamines cause and what can it be caused by?
Gut cancer proven in animals
What cancer do alkylating agents cause and what can it be caused by?
Leukaemia which has a small risk in humans
How much of all cancers are viral carcinogens responsible for?
- 10-15%
- Most oncogenic viral infections don’t result in cancer
What are examples of DNA viruses that can cause cancer?
- Human Herpes Virus 8
- Epstein Barr Virus
- Hepatitis B Virus
- Human papillomavirus
- Merkle cell polyomavirus
What cancer can Human Herpes Virus 8 (HHV8) cause?
Kaposi sarcoma
What cancers can Epstein Barr Virus (EBV) cause?
- Burkitt lymphoma
- Nasopharyngeal carcinoma
What cancer can Hepatitis B virus (HBV) cause?
- Hepatocellular carcinoma
What cancer can Human papillomavirus (HPV) cause?
Squamous cell carcinomas of the cervix, penis, anus, head and neck
What cancer can Merkle cell polyomavirus (MCV) cause?
Merkle cell carcinoma
What cancer does HIV cause?
- Doesn’t cause any
What are examples of RNA viruses that can cause cancer?
- Human T-lymphotrophic virus
- Hepatitis C Virus
What cancer can Human T-lymphotrophic virus (HTLV-1) cause?
Adult T-cell leukaemia
What cancer can Hepatitis C Virus (HCV) cause?
Hepatocellular carcinoma
Is UV light ionising or non-ionising?
Non-ionising
What type of cancer does UV light cause?
Exposure to UVA or UVB increases risk of BCC (basal cell carcinoma), melanoma, SCC (squamous cell carcinoma)
Who has increased risk from UV light?
- People with xeroderma pigmentosum
- Where normal intracellular DNA damage repairing mechanism is impaired
What effects does ionising radiation have?
- Long term effect
- Skin cancer in radiographers
- Lung cancer in uranium miners
- Thyroid cancer in Ukrainian children
What are examples of biological agents that can cause cancer?
- Hormones
- Mycotoxins
- Parasites
What hormones can cause cancer?
- Oestrogen
- Anabolic steroids
What cancer can be caused by an increase in oestrogen?
Mammary/endometrial cancer
What cancer can be caused by anabolic steroids?
Hepatocellular carcinoma (liver cancer)
What mycotoxin can cause cancer?
Aflatoxin B1
What cancer does aflatoxin B1 cause?
Hepatocellular carcinoma
What parasites can cause cancer?
- Chlonorchis sinensis
- Shistosoma
What cancer does Chlonorchis sinensis cause?
Cholangiocarcinoma
What cancer does Shistosoma cause?
Bladder cancer (particularly squamous cell carcinoma)
What are some other miscellaneous carcinogens?
- Asbestos
- Metals (arsenic → skin cancer)
What are host factors that could cause cancer?
- Ethnicity
- Diet / Lifestyle
- Constitutional factors - age, gender etc.
- Premalignant lesions
- Transplacental exposure
How does ethnicity influence cancer?
- ↑ Oral cancer in India, SE Asia (reverse smoking, betal nut chewing)
- ↓ Skin cancer in those with darker skin (melanin)
What are constitutional factors that influence cancer?
- Inherited predisposition
- Age
- Gender
How does inherited predisposition influence cancer?
- familial polyposis coli (chr 5)
- retinoblastoma (chr 13)
How does age influence cancer?
- incidence increases with age
- longer exposed to environment, live out latent period
How does gender influence cancer?
- breast cancer F:M = 200:1
How what lifestyle factors can influence cancer?
- Diet / Exercise
- Sexual behaviour
How does diet/ exercise influence cancer?
- Excess alcohol use increases risk of cancers of the mouth, oesophagus, liver, colon and breast
- Obesity increases risk of breast, oesophagus, colon and kidney cancer
- Exercise reduces risk of colon and breast cancer
How does sexual behaviour influence cancer?
- Unprotected sex increases risk of HPV-related cancer (cervix, penis, oropharyngeal)
What is a premalignant condition?
Identifiable local abnormality associated with increased risk of malignancy at that site
What are examples of premalignant conditions?
- Colonic polyps
- Cervical dysplasia (CIN)
- Ulcerative colitis
- Undescended testis
What is an example of transplacental exposure?
- Diethylstilboestrol → ↑ vaginal cancer
- Used to treat morning sickness, crosses placenta
