Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

EMS > Lecture 39: Familial cancer predisposition > Flashcards

Lecture 39: Familial cancer predisposition Flashcards

1
Q

True or false: All cancers are genetic but only a small proportion is caused by a high-risk hereditary cause.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Describe multi- stage carcinogenesis.

A

A series of genetic changes occur within cells leading to increasingly abnormal behaviour and histology

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

True or false: germ line mutations are more likely to enable cancer than somatic mutations

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Is it more likely for cancer to develop after a primary somatic mutation or a secondary somatic mutation?

A

Secondary somatic mutation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is Penetrance?

A

The percentage of individuals with a specific genotype who also express the expected phenotype

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Name two ways Penetrance may be modified?

A
  1. May be modified by other genetic variations
  2. May be modified by environmental factors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the role of gatekeeper genes?

A

they directly regulate tumour growth by monitoring and controlling cell division and death while preventing the accumulation of mutations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the role of caretaker genes?

A

improving genomic stability (repairing mutations)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the role of landscaper genes?

A

they control the stromal surrounding environment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What does the likelihood of developing cancer depend on?

A

The importance of the gene function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

A defect in which type of gene is associated with familial adenomatous polyposis?

A

Gatekeeper

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

A defect in which type of gene is associated with Lynch syndrome?

A

caretaker

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is another name for Lynch syndrome?

A

Hereditary nonpolyposis colorectal cancer (HNPCC)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

A defect in which type of gene is associated with juvenile polyposis syndrome:

A

landscaper

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the function of the tumour suppressor genes

A

Protects cells from becoming cancerous
Inhibit cell division, preventing the formation of tumours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What affect does loss of function of the tumour suppressor genes have?

A

Increases the risk of cancer.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the function of oncogenes?

A

Regulate cell growth and differentiation
Gain of function/activating mutations increase the risk of cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Give 5 examples of tumour suppressor genes:

A

1) APC

2) BRCA 1

3) BRCA 2

4) TP53

5) Rb

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Give 2 examples of oncogenes:

A

1) growth and signal transduction factor genes

2) RET gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the name of the theory that states that a cell requires both genes to be mutated for cancer to arise?

A

Knudson’s two hit hypothesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What does Knudson’s two-hit hypothesis state?

A

for a cell to become cancerous, two hits are required on a specific gene in a single cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Describe Knudson’s two hit hypothesis in inherited cancers:

A

one gene will already be affected due to inheritance meaning just one is required for cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What mode of inheritance do most familial cancers follow?

A

autosomal dominance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Give three examples of autosomal recessive familial cancers:

A

1) MUTYH associated polyposis

2) Fanconi anaemia

3) ataxia telangiectasia

Each parent is a carrier of one mutated copy, usually without the disease (but may have a different phenotype e.g. BRCA2)
¼ of children inherit both mutated copies and the cancer risk

25
Q

Give 6 mutation types associated with carninogenesis:

A

1) missense

2) nonsense

3) frame shift

4) splice site mutations

5) large deletions and duplications

6) translocations

26
Q

Do sporadic cancer mutations arise at young or old ages?

A

Old

27
Q

Do familial cancer mutations appear at young or old ages?

A

Young

28
Q

Name 6 ways of finding familial cancer genes

A

Disease-causing translocations may give locations
Studying sporadic cancer
Family studies – linkage analysis
Candidate gene analysis
Newer technologies e.g. whole exome sequencing
Focus now on ‘moderate risk’ genes and genetic modifiers

29
Q

Name the stages of a taking a family history

A

Include maternal and paternal sides

Consanguinity? Diagnoses in apparently unrelated people may be linked

At least 3 generations

Children, siblings, parents, uncles, aunts, nephews, nieces, grandparents, cousins

Types of cancer, age of diagnosis

Confirm if possible – medical records, cancer registries, death certificate

30
Q

Do sporadic cancer mutations commonly have one primary cancer or many?

A

One

31
Q

Do familial cancer mutations commonly have one primary cancer or many?

A

Many

32
Q

What gene is retinoblastoma associated with?

A

Rbl

33
Q

What are the purposes of genetic assessment?

A

Diagnosis/explanation of family history
Counselling of advantages and disadvantages of testing
Risk of further cancers for affected cases
Risk of cancer for unaffected relatives
Screening
Prevention
Treatment
Research

34
Q

What are the disadvantages of genetic assessment?

A

‘Can of worms’

Anxiety/unhappiness – self, children, other relatives

Genetic discrimination - ?? Not so much in UK

Results may not lead to any change in management

Financial costs to NHS (though has to be viewed as a whole)

35
Q

When is diagnostic testing used?

A

Initial diagnostic testing (mutational analysis) usually performed on DNA from a relative affected with cancer to try to identify the familial mutation

36
Q

When is predictive testing used?

A

If a mutation is identified in the family, predictive testing for the specific mutation may then be offered to other relatives to determine whether or not they are at risk

37
Q

What causes bilateral retinoblastoma?

A

germline mutations

38
Q

How many children are diagnosed with retinoblastoma a year in the UK?

A

30-50

39
Q

What is familial adenomatous polyposis?

A

the presence of hundreds of bowel polyps that appear from the teens onwards, giving a very high risk of bowel cancer

40
Q

Describe the presentation of retinoblastoma

A

Childhood ocular cancer
Very rare: 1 in 15,000-30000 live births
~30-50 children/year in UK
Classic example following Knudson 2-hit hypothesis
Retinoblastoma (Rb1) gene

41
Q

What 3 other cancers is famliial adenomatous polyposis associated with?

A

1) CHRPE (retinal disease)

2) desmoid tumour

3) osteomas

42
Q

What gene is familial adenomatous polyposis associated with?

A

APC (tumour suppressor gene)

43
Q

Describe the features of FAP

A

Hundreds of bowel polyps (adenomas) from teens onwards
Accounts for ~1% of bowel cancers
High risk (up to 100%) of bowel cancer if untreated (note attenuated form)
Other features – CHRPE, desmoid tumours, osteomas
APC tumour suppressor gene
Autosomal dominant inheritance
Colonoscopies, total colectomy late teens/early 20s

44
Q

What is Lynch syndrome?

A

Hereditary non-polyposis colorectal cancer

45
Q

What 5 mismatch repair genes is Lynch syndrome associated with?

A

1) MLH1

2) MSH2

3) MSH6

4) PMS2

5) EPCAM

46
Q

What other 4 cancers is Lynch syndrome associated with?

A

1) endometrial

2) ovarian

3) stomach

4) urinary tract

47
Q

What criteria is often used to diagnose familial Lynch syndrome in the family?

A

Modified Amsterdam Criteria

48
Q

How is Lynch sydnrome managed? (3)

A

1) colonoscopy every 2 months

2) removal of any polyps

3) aspirin

49
Q

What cancers are BRCA 1 and 2 mutations associated with? (5)

A

1) breast

2) ovarian

3) male breast cancer

4) pancreas

5) prostate

50
Q

What is the name of the surgery used to remove both ovaries and fallopian tubes?

A

bilateral salpingo-oopherectomy

51
Q

What gene mutation causes Li Fraumeni syndrome?

A

P53

52
Q

What is Li-Fraumeni syndrome?

A

Germline mutation of one copy of p53 causing a 100% lifetime risk of cancer

53
Q

What cancers is Li-Fraumeni syndrome associated with? (4)

A

1) breast

2) sarcomas

3) brain

4) leukaemia

54
Q

What is CHEK2 syndrome?

A

a mutation of the CHEK2 syndrome, giving a 22% lifetime risk of breast cancer

55
Q

How often should patients with Lynch syndrome have a colonoscopy?

A

every 24 months from age ~25 or 35 (gene dependent

(Removal of polyps/early detection of cancer improves survival
Role of aspirin in preventing polyps)

56
Q

How often should women get a breast screening?

A

annual MRI 30-50, annual mammography from 40 onwards (some eligible for screening from 25)

57
Q

What is the benefit of breast screenings?

A

Risk-reducing mastectomies +/- reconstruction
Risk-reducing BSO (ovarian screening probably no use)
Lifestyle changes
Pharmacological prevention BRCA2 (limited evidence)

58
Q

What are your risk of cancers with BRCA1 and BRCA 2 genes?

A

Risk of breast cancer 70%; ovarian BRCA1 – 44%; BRCA2 – 10-20%
Some increased risk of other cancers – e.g. prostate, male breast cancer, pancreas

59
Q

What are the function of BRCA1 and BRCA2 genes?

A

BRCA1&2 are involved in DNA repair

EMS (54 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions