Genetic Predisposition to Cancer

Question 1

What is the normal purpose of tumour suppressor genes?

Answer 1

Inhibit progression through the cell cycle, promote apoptosis or act as stability genes

Question 2

Mutations in tumour suppressor genes cause loss of function. T/F?

Answer 2

True

Question 3

Mutations in proto-oncogenes genes cause loss of function. T/F?

Answer 3

False - these cause a gain in function

Question 4

What are stability genes?

Answer 4

A type of tumour suppressor gene which acts to minimise genetic alterations and account for the most common hereditary cancer predisposition syndromes

Question 5

What is the normal purpose of proto-oncogenes genes?

Answer 5

Stimulate the cell cycle

Question 6

What factors differentiate familial cancers from sporadic cancers?

Answer 6

They are more uncommon, have an earlier age of onset and often cause multiple primary tumours

Question 7

What mode of inheritance is most common for inherited predispositions to cancer?

Answer 7

Autosomal dominant

Question 8

Most familial cancers are due to the inheritance of an altered proto-oncogene. T/F?

Answer 8

False - they are usually due to the inheritance of an altered tumour suppressor gene

Question 9

Both alleles of a proto-oncogene need to be affected in order for cancer to occur. T/F?

Answer 9

True

Question 10

Since both alleles of a proto-oncogene need to be affected in order for cancer to occur, there must be subsequent inactivation of the normal allele during the individual’s lifetime as well as the inheritance of a faulty tumour suppressor gene in order for cancer to occur. T/F?

Answer 10

True

Question 11

On which chromosome is the BRCA1 gene located?

Answer 11

Chromosome 17

Question 12

On which chromosome is the BRCA2 gene located?

Answer 12

Chromosome 13

Question 13

BRCA1 and BRCA2 are tumour suppressor genes. What is the normal function of these gene’s products?

Answer 13

Homologous recombination of double strand breaks (DNA repair)

Question 14

Mutations in BRCA1 and BRCA2 have approximately what penetrance for breast cancer?

Answer 14

80%

Question 15

As well as breast cancer, what other type of cancer do mutations in BRCA1 and BRCA2 predispose to?

Answer 15

Ovarian cancer

Question 16

The presence of male breast cancer within a family suggests the involvement of mutations in which gene?

Answer 16

BRCA2

Question 17

As well as the inheritance of mutated BRCA1 and BRCA2 genes, what genes can impact the likelihood of developing breast cancer?

Answer 17

Modifier genes (over 70 identified for BRCA1 and 2)

Question 18

Other than BRCA1 and BRCA2 mutations, mutations in which genes are less commonly associated with breast cancer?

Answer 18

TP53
PALB2
PTEN

Question 19

Individuals with BRCA1 and BRCA2 mutations can be offered what treatments?

Answer 19

Prophylactic masectomies and oopherctomies

Question 20

Individuals with BRCA1 and BRCA2 mutations are offered regular breast examinations and screening via mammograms and MRI. T/F?

Answer 20

True

Question 21

Screening for ovarian cancer is very difficult. T/F?

Answer 21

True

Question 22

Other than BRCA1 and BRCA2 mutations, mutations in which genes are associated with ovarian cancer?

Answer 22

HNPCC genes, RAD15, PTEN, STK11, PTCH

Question 23

What is the name of the syndrome which accounts for most cases of familial cancer?

Answer 23

Lynch synrome or hereditay non-polyposis colon cancers

Question 24

Lynch syndrome can result in colon cancer but also cancer of which other tissues?

Answer 24

Stomach
Uterus
Ovaries

Question 25

Lynch syndrome is caused by mutations in which genes?

Answer 25

MMR genes - MLH1 and MSH2

Question 26

What is the normal function of the MMR genes which are mutated in lynch syndrome?

Answer 26

Mismatch DNA repair

Question 27

What is the screenign regiment for those with lynch syndrome?

Answer 27

2 yearly colonscopies from age 25 | 2 yearly upper GI endoscopies from age 50

Question 28

Familial adenomatous polyposis is a rare cause of colon cancer. A mutation in which gene is responsible for this?

Answer 28

APC gene

Question 29

Familial adenomatous polyposis is a rare cause of colon cancer. What type of inheritance is exhibited in this condition?

Answer 29

Autosomal dominant

Question 30

Annual bowel screening is offered from what age to individuals with familial adenomatous polyposis?

Answer 30

11 years

Question 31

Familial adenomatous polyposis is associated with what condition of the eyes?

Answer 31

Congenital hypertrophy of the retinal pigment epithelium

Question 32

MYH-associated polyposis is a rare cause of colon cancer. What type of inheritance is exhibited in this condition?

Answer 32

Autosomal recessive

Question 33

MYH-associated polyposis is a rare cause of colon cancer. A mutation in which gene is responsible for this and what is its normal function?

Answer 33

MUTYH gene - base excision DNA reapair

Question 34

What screenign regime is offered to individuals with MUTYH mutations?

Answer 34

2 yearly - colonoscopies

Question 35

What is Li Fraumeni syndrome?

Answer 35

A rare autosomal dominant cancer predisposition syndrome

Question 36

What cancers does Li fraumeni syndrome predispose to?

Answer 36

``` Breast cancer Brain tumours Sarcomas Leukaemia Adrenocortical carcinomas ```

Question 37

A mutation in which gene is responsibe for Li Fraumeni syndrome?

Answer 37

TP53

Question 38

What is Cowden syndrome?

Answer 38

An autosomal dominant condition which causes an increased lifetime risk of breast, thyroid, uterine and other cancers