Genetics - predisposition to cancer

Question 1

Clinical approach to management of cancer and predisposing syndromes, including FAP, breast, ovarian and colon cancer.

Risk estimation for those at moderate risk, role of genetic testing.

Low penetrance genes and future possibilities.

Answer 1

.

Question 2

List the causes of CRC from most common to least common (5)

Answer 2

Sporadic
Familial
Lynch syndrome (aka HNPCC)
Familial adenomatous polyposis (FAP)
Rare CRC syndromes

Question 3

Cancer arises what either … or … mutations

Answer 3

germline or somatic (non-inheritable)

Question 4

Oncogenes affect which phase of the cell cycle

Answer 4

G1 (cell growth phase) of interphase (before mitotic phase)

Question 5

Tumour supressor genes affect which phase of the cell cycle

Answer 5

Prevent G1 (cell growth) from progressing into S (DNA replication) phase

Question 6

DNA repair genes affect which phase of the cell cycle

Answer 6

S (DNA replication) phase

Question 7

List the phases of the cell cycle

Answer 7

Interphase - G1, G0, S, G2

Mitotic phase - prophase, metaphase, anaphase, telophase, cytokinesis

Question 8

With oncogenes, how many mutations on a chromosome is enough for cancer development

Same question for tumour suppressor genes

Answer 8

1 for oncogenes

2 for tumour supressor genes, 1 makes you a susceptible carrier

Question 9

What is the main mechanism for familial cancers

Answer 9

Faulty DNA mismatch repair genes so mutation introduced by unrepaired DNA

Question 10

What is the mechanism for lynch syndrome (aka HNPCC)

Answer 10

Mutation in mismatch repair genes

Question 11

Is Lynch syndrome autosomal dominant or recessive

Answer 11

Autosomal dominant

Question 12

Lynch syndrome most commonly gives rise to CRC, what other cancers can it give rise to?

Answer 12

Endometrial (next commonest), gastric, biliary tract, ovarian, breast, small bowel (intestinal), urinary tract and more

Question 13

What cancers do the BRCA genes increase risk of in males

Answer 13

Prostate

Breast

Question 14

What is mendelian inheritance + what are the 4 modes of mendelian inheritance

Answer 14

The manner by which genes and traits are passed from parents to their children

Autosomal dominant, autosomal recessive, X-linked dominant, and X-linked recessive

Question 15

When to suspect hereditary cancer syndromes like Lynch syndrome

Answer 15

Cancer in 2 or more close relatives on same side of family

Young age diagnosis

Multiple primary tumours

Bilateral or rare cancers

Characteristic pattern of tumours, e.g. breast + ovary

Evidence of autosomal dominant transmission

Question 16

What’s more common - hereditary or sporadic cancers

Answer 16

Sporadic

Hereditary cancers are quite a small proportion

Question 17

4 steps in the process of cancer genetics

Answer 17

Obtain detailed family history
Confirm diagnoses of cancer
Risk estimation
Counselling

Question 18

Consider genetic testing in what group of people

Answer 18

High risk, not low or moderate (estimate risk for these)

Question 19

BRCA1/2 gene carriers can get what prophylactic procedures

Answer 19

Mastectomy - significantly reduces breast cancer risk in those with a FH of it

Ooophorectomy - eliminates risk of primary ovarian cancer, but induces menopause early

Question 20

A gene carrier of CRC is recommended to get a colonoscopy how frequently

Answer 20

2 yearly from 25

Question 21

Someone with a moderate risk of CRC is recommended to get a colonoscopy how frequently

Answer 21

5 yearly from 50

Question 22

Ways to genetically test for Lynch syndrome (2)

Answer 22

Immunohistochemistry (IHC) for mismatch repair genes

Microsatellite instability testing (MSI)

Question 23

What prophylactic drug can be given to prevent CRC

Answer 23

Aspirin

Question 24

Benefits of genetic testing

Answer 24

Identifies highest risk

Identifies non-carriers in families with a known mutation

Allows early detection and prevention strategies

May relieve anxiety

Question 25

Limitations of genetic testing

Answer 25

Does not detect all mutations

Continued risk of sporadic cancer

Efficacy of interventions variable

May result in psychosocial or economic harm

Question 26

What does low penetrance mean

Answer 26

If some people with the mutation do not develop features of the disorder, the condition is said to have reduced (or incomplete) penetrance