Carcinogenesis

Question 1

Carcinogenesis

Answer 1

Transformation of normal cells to neoplastic cells by causing permanent genetic alterations.

Question 2

Carcinogen

Answer 2

An environmental agent participating in the causation of tumours.

Can be carcinogenic (cancer causing) these are also mutagenic or oncogenic (tumours causing).

Question 3

Multistep carcinogenesis hypothesis

Answer 3

More than one carcinogen is necessary for the complete neoplastic transformation of a cell.

Question 4

Hit-and-run situation

Answer 4

Specific causative agent is not usually found in the eventual tumour.

Question 5

Why is it difficult to identify a single causative factor of CA?

Answer 5

Long time interval between exposure to a carcinogen and the appearance of signs and symptoms = latent interval.

Question 6

Carcinogens can be identified from

Answer 6

Epidemiological studies

Assessment of occupational risks

Direct accidental exposure

Carcinogenic effects in laboratory animals

Transforming effects on cell cultures

Mutagenicity testing in bacteria

Question 7

Carcinoma of the cervix is associated with what genotypes of HPV?

Answer 7

16 & 18.

Question 8

Since carcinogens are not united by any common physical or chemical properties, what needs to be done to check their safety…

Answer 8

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.

Question 9

What are the main classes of carcinogenic agents?

Answer 9

Chemicals

Viruses

Ionising radiation

Non-ionising radiation

Exogenous hormones

Bacteria/fungi/parasites

Miscellaneous agents

Question 10

Chemical carcinogens

Answer 10

Some directly damages

Some requires metabolic conversion (procarcinogen) -> ultimate carcinogen.

Question 11

Oncogenic viruses

Answer 11

Oncogenic DNA viral genome - directly incorporated into host DNA.

Oncogenic RNA viral genome - reverse transcriptase - then incorporated.

Question 12

HHV8

Answer 12

Kaposi sarcoma

Question 13

EBV

Answer 13

Burkitt lymphoma, nasopharyngeal carcinoma

Question 14

HBV

Answer 14

Hepatocellular carcinoma

Question 15

HPV

Answer 15

Squamous cell carcinomas of the cervix, penis, anus, head and neck

Question 16

MCV (Merkel cell polyomavirus)

Answer 16

Merkel cell carcinoma

Question 17

HTLV-1 Human T-lymphotrophic virus

Answer 17

Adult T-cell leukaemia

Question 18

HCV

Answer 18

Hepatocellular carcinoma

Question 19

Why is UVC not causing CA?

Answer 19

It is reflected by the atmosphere so never reaches the surface.

Question 20

Which type of UV light is a bigger causal factor?

Answer 20

UVB>UVA

Question 21

Host factors in carcinogenes

Answer 21

Race
Diet
Constitutional factors
Premalignant lesions and conditions
Transplacental exposure

Question 22

Multiple endocrine neoplasia (MEN) syndromes

Answer 22

Endocrine tumours.

Autosomal dominant MEN1 gene on Cr. 11 and RET gene on Cr. 10

Question 23

Xeroderma pigmentosum

Answer 23

Skin cancers.

Autosomal recessive XP genes.

Question 24

Familial adenomatous polyposis coli (FAP)

Answer 24

Colorectal adenomas and adenocarcinomas.

Autosomal dominant; APC gene on Cr. 5

Question 25

Hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome

Answer 25

Colorectal carcinoma and other tumours (endometrium, ovary…)

MLH1 on Cr. 3
MSH2 on Cr. 2
Autosomal dominant

Question 26

von Hippel-Lindau syndrome

Answer 26

Renal cell carcinoma, phaeochromocytoma…

Autosomal dominant VHL gene on Cr 3.

Question 27

Li-Fraumeni syndrome

Answer 27

Breast carcinoma

Autosomal dominant mutant p53 on Cr 17

Question 28

Retinoblastoma syndrome

Answer 28

Retinoblastoma

Autosomal dominant RB1 gene on Cr 13

Question 29

Familial brast carcinoma

Answer 29

Breast carcinoma, ovarian carcinoma
Autosomal dominant.

BRCA1 on Cr 17
BRCA2 on Cr 13

Question 30

Fanconi anaemia (FA)

Answer 30

Leukaemia

Autosomal recessive FANC gene