11. Cancer Genetics

Question 1

cancer

Answer 1

a disorder of cell growth
caused by alterations in genes which control cell growth

Question 2

germline mutations

Answer 2

present in sperm or egg
are heritable
cause cancer family syndromes

Question 3

somatic mutations

Answer 3

occur in non germline tissues
are nonheritable

Question 4

who is at risk to hereditary cancer

Answer 4

hereditary cancers account for only a small proportion of all cancer

Question 5

the cancer family history is the key to:

Answer 5

accurate risk assessment
effective genetic counselling
appropriate medical follow-up

Question 6

when to suspect hereditary cancer syndrome

Answer 6

• cancer in 2 or more close relatives
• early age diagnosis
• multiple primary tumours
• bilateral or multiple rare cancers

Question 7

incomplete penetrance

Answer 7

when you have the gene alteration but never show it (symptoms)

Question 8

what are the two ways of classifying hereditary cancer

Answer 8

by tumour type
by type of gene mutated

Question 9

what are the two main groups of tumour types

Answer 9

rare hereditary cancer syndromes

subset of common cancers which is hereditary, eg. colon cancer, breast cancer, ovarian cancer

Question 10

what are the three type of genes that can be mutated

Answer 10

tumour suppressor genes
oncogenes
DNA damage-response genes

Question 11

explain tumour suppressor genes

Answer 11

they slow down cell growth (like breaks)

cancer arises when both breaks fail

Question 12

Retinoblastoma

Answer 12

tumour that develops in the pigment cells in the back of a childs eye

• occurs in heritable and nonheritable forms
• autosomal dominant transmission

Question 13

non heritable retinoblastoma

Answer 13

• unilateral tumour
• no family history
• avg age of diagnosis is 2+

Question 14

heritable retinoblastoma

Answer 14

• bilateral tumour
• 20% of cases have family history
• avg age of diagnosis is less than 1

Question 15

familial adenomatous polyposis

Answer 15

• autosomal disorder, fully penetrant
• development of multiple initally benign colonic polyps and if untreated will progress into colon cancer

Question 16

what is the treatment of familial adenomatous polyposis

Answer 16

to remove the colon

Question 17

oncogene

Answer 17

accelerate cell division

normal genes regulate cell growth but when there is one mutation it leads to accelerated cell division

Question 18

multiple endocrine neoplasia type 2 (MEN2)

Answer 18

inherited disorder of oncogene

Question 19

what are three specific subtypes of the condition

Answer 19

thyroid C cell tumors,
parathyroid adenomas,
adrenal medulla tumors

Question 20

common clinical disorder of DNA repair genes

Answer 20

common subset of colon cancer
HNPCC is due to defects in DNA mismatch repair

Question 21

clinical features of HNPCC

Answer 21

early but variable age at CRC (colorectal cancer) diagnosis
tumour site in proximal colon predominates (majority of the cancer is in the upper part of the colon)

Question 22

MSI - microsatellite instability

Answer 22

due to mismatch repair failure

Question 23

what are the benefits of predictive genetic testing

Answer 23

• identifies those who are not at risk
• saves on screening resources

Question 24

what is the intervention and recommendation for colorectal cancer

Answer 24

colonoscopy
begin at age 20-25 and repeat every 1-2 years

Question 25

what is the intervention and recommendation for endometrial cancer

Answer 25

transvaginal ultrasound or endometrial aspirate annually, starting at age 25-35

Question 26

how much breast cancer is hereditary

Answer 26

5-10%

Question 27

how much ovarian cancer is hereditary

Answer 27

15-20~%

Question 28

what are some features that indicate increased likelihood of having BRCA mutations

Answer 28

- multiple cases of early onset breast cancer - ovarian caner - breast and ovarian cancer in the same woman - bilateral breast cancer - ashkenazi jewish heritage - male breast cancer

Question 29

BRCA 1

Answer 29

tumour suppressor gene on chromosome 17 autosomal dominant transmission

Question 30

what is the lifetime risk of the cancers associated with BRCA1

Answer 30

breast cancer 50-85% second primary breast cancer 40-60% ovarian cancer 15-45%

Question 31

what is the lifetime risk of the cancers associated with BRCA2

Answer 31

breast cancer 50-85% male breast cancer 6% ovarian cancer 10-20%

Question 32

what are the benefits of BRCA testing

Answer 32

- identifies high risk individuals - identifies noncarriers in families with a known mutation - allows early detection and prevention strategies - may relieve anxiety - may allow targeted chemo

Question 33

risk and limitations of BRCA testing

Answer 33

- does not detect all mutations - continued risk of sporadic cancer - efficacy of interventions unproven - may rest is psychosocial or economic harm

Question 34

surveillance options for breast cancer in healthy BRCA mutation carriers

Answer 34

monthly breast self exams (begin age 18) and early clinical surveillance (begin age 25)