Cancer biology

Question 1

What is cancer?

Answer 1

Loss of control of normal cell proliferation, differentiation + death

Involves a gain of function in proto-oncogenes due to mutation (e.g. ras)/amplification (e.g. HER2)/translocation (e.g. BCR-ABL)
– plus some of the things below:
*Loss of function in tumour suppressor genes
*Genes at cell cycle checkpoint
*Genes for DNA repair, apoptosis, growth factor receptros
etc

Question 2

Why is cancer more common with age?

Answer 2

DNA damage accumulates + less is repaired by the normal mechanisms

Question 3

What are the 6 hallmarks of cancer?

Answer 3

1. Evasion of apoptosis
2. Self-sufficient growth signals
3. Insensitive to anti-growth signals
4. Angiogenesis (facilitated by tumour cells + host inflammatory cells)
5. Limitless replicative potential
6. Tissue invasion + metastasis

Question 4

What features indicate an inherited cancer?

Answer 4

3 affected relatives with the same/associated cancers
2 generations affected
1 person <50y (at least)

Question 5

Autosomal dominant bowel cancer genetic syndromes?

Answer 5

• HNPCC/Lynch syndrome: most linked to colon + endometrial cancers (also can cause others)
• FAP: APC gene, >100 colonic adenomas (then adenocarcinoma), also a/w upper GI tumours

Question 6

AD breast + ovarian cancers

Answer 6

• BRCA1 a/w triple negative breast cancer in young women
• BRCA2 more a/w post-menopausal BC (but also higher risk of younger onset), typically good hormone response
• BRCA genes implicated in 50% of male breast cancer
• Strongly a/w ovarian cancers, also increase risk of other cancers

Question 7

Multiple endocrine neoplasia syndromes

Answer 7

MEN1: pituitary, parathyroid, pancreas
MEN2a: medullary thyroid, phaeochromocytoma + parathyroid
MEN2b: medullary thyroid, pheochromocytoma and Marfanoid habitus/mucosal neuroma

Question 8

Neurofibromatosis type 1

Answer 8

Neurofibromas, optic nerve glioma, neurofibrosarcoma

Question 9

Familial retinoblastoma

Answer 9

RB1 gene, often b/l

Question 10

Von Hippel-Lindau syndrome

Answer 10

Malignant + benign tumours and cysts e.g. haemangioblastomas, kidney/pancreas/genital cysts, pheochromocytoma, endolymphatic sacs in inner ear causing tinnitus, renal clear cell carcinoma

Question 11

Li-Fraumeni syndrome

Answer 11

Higher risk of many cancers inc of soft tissue, osteosarcoma, breast, CNS, acute leukaemias

Question 12

Autosomal recessive cancer syndromes

Answer 12

Xeroderma pigmentosa
Ataxia telangiectasia - NHL, leukaemia
Fanconi’s anaemia + Bloom’s syndrome - lymphoma/leukaemia

Question 13

What environmental factors can induce carcinogenesis?

Answer 13

• Tobacco: lung, oral/larynx/oesophagus/bladder
• Alcohol: upper respiratory tract, GI, breast
• Diet: low fat + processed red meats (deffo bowel); obesity-oestrogenic stimulation of breast + endometrium
• UV light
• Arsenic in water - lung + colon (issue in SE Asia)
• Occupational e.g. asbestos, polycyclic hydrocarbons (skin, lung, bladder), benzene (MDS, myeloma)
• Infection: e.g. HBV+HCV (HCC), EBV (Burkitt’s lymphoma, nasopharyngeal carcinoma), HIV (lymphoma-EBV, Kaposi’s sarcoma-HHV8), HPV 16 + 18 (cervix, 16-oral)
• Meds: oestrogens (breast, endometrial), cytotoxic drugs (esp AML bladder liver)
• Radiation: leukaemia, thyroid, breast. Like accidents, diagnostic imaging (cumulative + dose-dependent, so children higher risk)

Question 14

What are familial cancer syndromes?

Answer 14

When there are gremline mutations in egg/sperm cells, present in all tissues

Carcinogenesis depends on penetrance of gene + whether is dominant or recessive; carriers are at risk from the syndrome but usually need further mutations to develop cancer