5 Familial cancer syndromes

Question 1

Differentiate between caretaker genes, gatekeeper genes and landscaper genes.

Answer 1

Caretaker: DNA repair and carcinogen metabolism.
Gatekeeper: cell cycle control and programmed cell death.
Landscaper: control the surrounding stromal environment.

Question 2

Define penetrance.

Answer 2

Percentage with a gene change who develop the condition.

Question 3

What are tumour suppressor genes and how do they lead to cancer? 4 examples.

Answer 3

Protects cells from becoming cancerous. Loss -> cancer.

APC, BRCA1/2, TP53, Rb.

Question 4

What do oncogenes do?

Answer 4

Regulate cell growth and differentiation, gain of function increases cancer risk.

Question 5

Name 3 cancer syndromes that show an autosomal recessive inheritance pattern. How do these appear in a family tree?

Answer 5

MYH associated polyposis.
Fanconi anaemia.
Ataxia telangiectasia.
Sporadic, may appear to skip generations.

Question 6

Differentiate between a missense and nonsense mutation.

Answer 6

Missense - different amino acid.

Nonsense - shortened protein.

Question 7

Differentiate between the presentation of a sporadic vs familial cancer.

Answer 7

Sporadic - older onset, one cancer, family unaffected, non genetic cancers (cervix, lung).
Familial - younger onset, multiple primaries, family affected, genetically related cancers.

Question 8

Explain genetic basis of retinoblastoma.

Answer 8

Rb1 gene following Knudson’s 2 hit hypotheses. Bilateral cases are germline. 15% of unilateral are germline due to high new mutation rate.

Question 9

Explain the genetic basis of familial adenomatous polyposis. Which gene?

Answer 9

100% risk of bowl cancer if untreated. APC tumour suppressor gene, AD inheritance.

Question 10

What is the cancer risk in Hereditary Non-Polyposis Colorectal Cancer?
How is it inherited?

Answer 10

60-80% risk of bowl adenomas or cancers.

Autosomal dominant.

Question 11

What are the amsterdam criteria for HNPCC?

Answer 11

One member diagnosed before 50yo. 
Two generations affected. 
Three affected relatives (one first degree).
FAP excluded. 
Pathologic examination verifies tumours.

Question 12

BRCA1/2 raise the risk of which cancers?

Answer 12

Breast: 80%.
Ovarian 1:40% 2:20%
Prostate, melanoma, male breast cancer.

Question 13

Li Fraumeni Syndrome; gene: inheritance: lifetime risk:

Answer 13

P53 mutations. Autosomal dominant. 100% lifetime risk of cancer.

Question 14

Which syndrome does PTEN lead to?

Cancers? (4).

Answer 14

Cowden.

Breast, endometrial, thyroid, renal.

Question 15

Which syndrome does STK11 lead to?

Cancers? (2).

Answer 15

Peut Jeghers.

GI tract, breast.

Question 16

Gene in Von Hippel Lindau syndrome?

Cancers? (3).

Answer 16

VHL

Renal, haemangioblastoma, phaeochromocytoma.

Question 17

Besides bowel cancer, what is FAP associated with? (3).

Answer 17

Raises CHRPE, desmoid tumour and osteoma risk.

Question 18

What condition do these genes lead to?
MLH1, MSH2, MSH6, PMS 1/2.
What type of genes are they?

Answer 18

HNPCC.

Mismatch repair genes.

Question 19

Which cancers does Li Fraumeni syndrome predispose people to? (5).

Answer 19

Leukaemia.
Adrenocortical.
Breast.
Brain.
Sarcoma.

Question 20

Besides retinoblastoma, what does the RB1 gene raise your risk for?

Answer 20

Osteosarcoma.

Question 21

What type of genes are these…

Growth and signal transduction genes, RET gene?

Answer 21

Oncogenes.