Genetics Predisposition to Cancer

Question 1

What do a small proportions of cancers happen due to?

Answer 1

Increased inherited predisposition to cancer (genetic)

Question 2

What are the 2 different kinds of gene mutations that cancer can arise from?

Answer 2

Somatic mutations

Germline mutations

Question 3

Where to somatic mutations occur?

Answer 3

In somatic tissue, nongermline

Question 4

What can you say about the inheritability of somatic and germline mutations?

Answer 4

Somatic cannot be inherited and germline can

Question 5

Where are germline mutations present?

Answer 5

In egg or sperm

Question 7

What are some genetic processes associated with cancer?

Answer 7

Oncogenes

Tumour suppresor genes

DNA damage response genes

Question 8

What are proto-oncogenes?

Answer 8

Normal gene that codes for proteins to regulate cell growth and differentiation

Question 9

What can mutations change into oncogenes and what does this do?

Answer 9

Proto-oncogenes which accerlerates cell division

Question 10

What are tumour suppresor genes?

Answer 10

Genes that inhibit cell cycle or promotes apoptosis

Question 11

What happens when tumour suppresor genes fail?

Answer 11

Cancer arises

Question 12

What are DNA damage response genes?

Answer 12

Repair mechanism for DNA

Question 13

What happens when DNA damage response genes fail?

Answer 13

Cancer arises due to speeding the accumulation of mutations in other critical genes

Question 14

What is an example of a DNA damage response gene?

Answer 14

Mismatch repair genes (MMR genes)

Question 15

What do mismatch repair (MMR) genes do?

Answer 15

Corrects errors that spontaneously occur during DNA replication like single base mismatches or short insertions and deletions

Question 16

What does mismatch repair failure lead to?

Answer 16

Microsatellite instability (MSI) where there is the addition of nucleotide repeats, which is the phenotypic evidence that MMR is not functioning normally

Question 17

What is microsatellite instability (MSI)?

Answer 17

Where there is an addition of nucleotide repeats, which is phenotypic evidents that mismatch repair genes (MMR) are not working correctly

Question 18

What are the 3 kinds of tumours?

Answer 18

Benign

Malignant

Dysplastic

Question 19

What are some properties of benign tumours?

Answer 19

Lack the ability to metastasize

Rarely or never become cancerous

Can cause negative health benefits due to pressure on other organs

Question 20

What are some properties of dysplastic tumours?

Answer 20

Benign but could progress to malignancy

Cells show abnormalities of appearance and cell maturation

Question 21

What is a unique property of malignant tumours?

Answer 21

Able to metastasize

Question 22

What are some other causes of cancer in relation to genes?

Answer 22

Autosomal recessive syndromes

Multiple modifier genes of lower genetic risk

Question 23

What are de novo mutations?

Answer 23

Occur in germ cells of parents with no family history of hereditary cancer syndrome

Question 24

What are de novo mutations common in?

Answer 24

Famial adenomatous polyposis

Multiple endocrine neoplasia 2B

Hereditary retinoblastoma

Question 25

What is hereditory retinoblastoma?

Answer 25

Most common eye tumour in children

Question 26

What is the type of inheritence of most cancer susceptability genes?

Answer 26

Dominant

Question 27

What are some risk factors for breast cancer?

Answer 27

Ageing Family history Late menopause Early menarche Nulliparty (condition where woman cannot give birth) Estrogen use Dietary factors (alcohol) Lack of exercise

Question 29

What is nulliparty?

Answer 29

Condition where woman cannot give birth

Question 30

What are some genes that increase hereditory susceptability to breast cancer?

Answer 30

BRCA1 BRCA2 TP53 PTEN

Question 31

Which of BRCA1 and BRCA2 increases the risk of breast cancer the most?

Answer 31

BRCA1 (20-40%) whereas BRCA2 is only 10-30%

Question 32

What are functions of the BRCA1 gene?

Answer 32

Checkpoint mediatory DNA damage signalling and repair Chromatin remodelling Transcription

Question 33

What is the main function of the BRCA2 gene?

Answer 33

DNA repair by homologous recombination

Question 34

What do BRCA1 mutations increase the risk of?

Answer 34

Breast cancer (50-85%) Second primary breast cancer (40-60%) Ovarian cancer (15-45%) Other cancers

Question 35

What do BRCA2 gene mutations increase the risk of?

Answer 35

Breast cancer (50-85%) Ovarian cancer (10-20%) Male breast cancer (6%) Other cancers

Question 36

What are some risk factors for colorectal cancer?

Answer 36

Ageing Personal history of colorectal cancer or adenomas High fat, low fibre diet Inflammatory bowel disease Family history of colorectal cancer

Question 37

What are the 2 possible hereditary colorectal cancer syndromes?

Answer 37

Non-polyposis (few to no adenomas) Polyposis (multiple adenomas)

Question 38

What is an example of a non-polyposis hereditary colorectal cancer?

Answer 38

HNPCC

Question 39

What are examples of polyposis hereditary colorectal cancers?

Answer 39

FAP AFAP MAP

Question 40

What are adenomas?

Answer 40

A beneign tumour formed from glandular structures in epithelial tissue

Question 41

What are some clinical features of HNPCC?

Answer 41

Early but variable age in CRC diagnosis (about 45 years) Tumour site through colon rather than descending colon

Question 42

What is a clinical feature of familial adenomatous polyposis (FAP)?

Answer 42

Risk of extracolonic tumours (upper GI, thyroid, brain)

Question 43

What is a milder form of FAP?

Answer 43

Recessive MYH polyposis

Question 44

What do multiple modifier genes of lower genetic risk explain?

Answer 44

Families with history of cancer and no identified mutation Different in cancer penetrance in families with the same mutation

Question 45

What can cancer risk for patients with FAP be managed by?

Answer 45

Surveillance Surgery Chemoprevention

Question 46

What are predictive gene tests used for?

Answer 46

To test who has genes that are associated with an increased risk in developing cancer

Question 47

What is it important to remember about inherited mutations causing cancer compared to other causes?

Answer 47

Most cancers are sparodic, with only a small proportion being due to inherited mutations