5b: Sporadic And Familial Cancers

Question 1

T or F: There is no genetic risk involved in sporadic cancers

Answer 1

False, there is an inherited risk, but there may be no evidence of family history

Question 2

How did they study the effects of heritable and environmental factors of different cancers?

Answer 2

Observed pairs of identical twins, who had same genes and similar environments.

Question 3

Why may inherited cancer syndromes have other manifestations other than cancer?

Answer 3

The gene is mutated in all cells, and tissues may respond differently in their phenotype/ presentation of the mutations. May be cancer, may be something else.

Question 4

What is an example of a syndrome with an increased colorectal cancer risk caused by an inherited mutation

Answer 4

JPS - juvenile polyposis syndrome

Question 5

What is the difference between familial and sporadic cancers in terms of mutations?

Answer 5

In familial cancers, the first mutation is inherited, so less successive clonal sweeps with selected mutations is needed for the development of the tumour.
This results in earlier development of the cancer compared to sporadic.

Question 6

What % of cancers arise as part of a family cancer syndrome

Answer 6

2-5%

Question 7

What are the most common syndromes that cause familial CRC?

Answer 7

• Familial adenomatous polyposis (FAP)
• Lynch syndrome
• MYH and proofreading polymerase associated polyposis

Question 8

What is the alternative name for Lynch Syndrome?

Answer 8

Hereditary non-polyposis

Question 9

Fill in the blanks:
FAP and LS arise from ____-__-____ mutations of specific genes.
They are autosomal _____.
The genes mutated have _____ effects.

Answer 9

1) loss-of-function
2) dominant
3) pleiotropic

Question 10

What is the penetrance of LS and FAP?
Why might this not be accurate?

Answer 10

LS - 90%
FAP - 100%
The data used is old, newer screening has detected abherrant mismatch repair without CRC.

Question 11

What gene, what location, and what type of mutation causes FAP?

Answer 11

• APC gene
• 5q21
• truncation

Question 12

What is te characteristic phenotype of FAP?

Answer 12

Development of 100s-1000s of intestinal adenomas

Question 13

What age does cancer tend to arise around in patients with FAP?

Answer 13

Around 40

Question 14

List a few extra-colonic manifestations associated with FAP

Answer 14

• small bowel and gastric tumours
• desmoids (malignant fibroblasts)
• CHRPE (Congenital Hypertrophy of the Retinal Pigment Epithelium)
• Osteoma
• Jaw cyst
• Thyroid tumours
• Hepatoblastoma

Question 15

At which site in the chromosome does severe FAP phenotype arise when mutated and why?

Answer 15

• Mutation cluster region
• Gives mutation the best select advantage. Truncates protein, losing the ability to bind/regulate B-catenin

Question 16

What is meant by “attenuated FAP”

Answer 16

Polyposis is present, but the number is different

Question 17

The mutation of which proteins causes Lynch syndrome?

Answer 17

One of the proteins that form the mismatch repair complex: MSH2, MLH1, PMS2, MSH6

Question 18

What is the median age for the onset of anger arising due to lynch syndrome?

Answer 18

42

Question 19

Fill in the blanks:
Tumours arising from Lynch syndrome show loss of _____ repair, manifesting as _____ _____.

Answer 19

1) mismatch
2 & 3) microsatellite instability