Inherited colorectal cancer

Question 1

Two main inherited colorectal cancers

Answer 1

Lynch syndrome and FAP

Question 2

Lynch syndrome/HNPCC same thing, what does HNPCC stand for?

Answer 2

Hereditary non polyposis colorectal cancer

Question 3

What other cancers do individuals with Lynch syndrome have a risk of

Answer 3

rectum, stomach, small intestine, liver, brain, ovaries and uterus (endometrium)

Question 4

Do individuals with Lynch get polyps?

Answer 4

May get some benign polyps, these may happen earlier than in the general population but not in greater numbers

Question 5

Inheritance pattern of Lynch syndrome

Answer 5

Autosomal dominant

Question 6

What genes are affected in individuals with Lynch syndrome

Answer 6

MLH1, MSH2, MSH6 and PMS2 (all mismatch repair genes)

Question 7

What happens when mismatch repair genes are defective?

Answer 7

They cannot repair cell damage

Question 8

Cells that lack normal MMR can acquire additional mutations such as

Answer 8

MSI

Question 9

What is MSI?

Answer 9

Change in the length of nucleotide repeat sequences

Question 10

What percentage of patients with Lynch syndrome have MSI?

Answer 10

90%

Question 11

What percentage of patients with sporadic colorectal cancer have MSI?

Answer 11

10-15%

Question 12

Testing strategy for Lynch syndrome

Answer 12

Pathology IHC MMR genes for loss of staining
If staining equivocal sent to Genetics for MSI, BRAF testing and MLH1 promoter methylation
If inherited Sanger sequence appropriate gene

Question 13

How do the genetics department perform MSI testing for Lynch?

Answer 13

PCR known areas of nucleotide repeat sequence, separate size fragments using capillary electrophoresis, GeneMarker to analyse

Question 14

How do the genetics department perform BRAF testing for Lynch?

Answer 14

Sanger sequencing, Mutation surveyor to analyse

Question 15

How do the genetics department perform MLH1 promoter methylation testing for Lynch?

Answer 15

Methylation specific MLPA (MS-MLPA)

Question 16

If individual with colorectal cancer has a BRAF mutation is it more likely to be inherited or sporadic?

Answer 16

Sporadic

Question 17

If individual with colorectal cancer has MLH1 promoter methylation is it more likely to be inherited or sporadic?

Answer 17

Sporadic

Question 18

What does FAP stand for?

Answer 18

Familial adenomatous polyposis

Question 19

What is FAP?

Answer 19

A cancer syndrome that could lead to development of colorectal cancer

Question 20

There is a variant of FAP what is this called?

Answer 20

Attenuated familial polyposis

Question 21

When do polyps arise in individuals with attenuated familial polyposis?

Answer 21

Polyp growth is delayed until around 55 years of age

Question 22

Number of polyps individuals with FAP get in colon

Answer 22

More than 100, could be thousands

Question 23

When do polyps arise in individuals with FAP?

Answer 23

Start to develop in mid-teens, have multiple by age 35

Question 24

Inheritance pattern of FAP and attenuated FAP?

Answer 24

Autosomal dominant

Question 25

Inheritance pattern of milder form of FAP?

Answer 25

Autosomal recessive

Question 26

Gene mutated in FAP and attenuated FAP?

Answer 26

APC (TS)

Question 27

Gene mutated in milder form of FAP?

Answer 27

MUTYH (TS)

Question 28

Testing performed on APC and MUTYH genes in FAP and milder form of FAP

Answer 28

Sanger sequencing

Question 29

Number of polyps individuals with the milder form of FAP get in their colon

Answer 29

Less than 100

Question 30

What other type of cancers do individuals with FAP have a risk of?

Answer 30

Stomach, pancreas, brain, thyroid and liver tumours in children