Clinical Cancer Genetics

Question 1

How long is the human genome?

Answer 1

➝ 3 billion BP

Question 2

What % of the human genome codes for genes?

Answer 2

➝ 2%

Question 3

What is DNA?

Answer 3

➝ A molecule which contains the human genetic code

Question 4

What are genes?

Answer 4

➝The instructions to tell the body how to grow, develop and function
➝Consist of sections of DNA which the cell translates into proteins

Question 5

How many genetic changes does one person have compared to another?

Answer 5

➝ 5 million different genetic changes

Question 6

What is the lifetime risk for developing cancer?

Answer 6

➝ 1 in 2

Question 7

What three types of cancer are there?

Answer 7

➝ Sporadic
➝ familial cancer
➝ high risk genes

Question 8

How do sporadic cancers arise?

Answer 8

➝ due to acquired (somatic) mutations within a cell that occur during replications

Question 9

What are the two internal changes that lead to sporadic cancers?

Answer 9

➝reactive oxygen species

➝ ineffective DNA repair mechanisms

Question 10

What are the 4 external changes that lead to sporadic cancer?

Answer 10

➝UV light
➝ ionising radiation
➝ cigarette smoke
➝chemical consumption

Question 11

What is inherited cancer risk?

Answer 11

➝ Genetic changes we are born with which increase the risk of developing cancer

Question 12

What types of inherited cancer risks are there?

Answer 12

➝ High risk changes
➝ moderate risk changes
➝ low risk changes

Question 13

If there is clustering of the same types of cancer in a family what is this called?

Answer 13

➝ multifactorial risk

Question 14

If you have a lot of common variants what does this mean?

Answer 14

➝ risk of cancer is pushed up from the normal distribution

Question 15

What are the high risk cancer predisposition genes for breast and ovarian cancer?

Answer 15

➝ BRCA

Question 16

What are the high risk cancer predisposition genes for prostate and pancreatic cancer?

Answer 16

➝ BRCA2

Question 17

What is the likelihood of having BRCA genes if you have breast or ovarian cancers?

Answer 17

➝ 5-10%

Question 18

What is the high risk cancer predisposition gene for colon cancer?

Answer 18

➝ Lynch

Question 19

What is multifactorial or polygenic risk?

Answer 19

➝ when you have multiple lower risk genetic variants

Question 20

How much genetic information do you share with your first degree relatives?

Answer 20

➝ 50%

Question 21

What are the 5 things you look at when assessing family history?

Answer 21

➝ Look at whether someone has had multiple cancers
➝Bilateral cancers e.g left kidney, right kidney
➝Look at the number of relatives that have had cancer
➝The types of cancer they have had
➝How close the family members are to each other

Question 22

What are the signs that breast cancer is likely to be genetic in a family?

Answer 22

➝If there are multiple individuals that develop premenopausal breast cancer there might be a genetic component
➝both ovarian and breast cancers in one family

Question 23

If you are older and develop breast cancer why is it less likely that it is genetic?

Answer 23

➝ the longer you live the more likely it is that cancer is sporadic

Question 24

What pathological subtypes of cancers increase the risk of having cancer predisposition genes and what genes are these?

Answer 24

➝ High grade serous ovarian cancer: BRCA1/2
➝Medullary thyroid cancer: RET
➝Triple negative breast cancer: BRCA1/2
➝Type 2 papillary kidney cancer: FH

Question 25

What is molecular testing and why is it done?

Answer 25

➝ Tumour testing | ➝ it may identify genetic changes which could indicate inherited risk

Question 26

What test is done if someone has colon cancer and why?

Answer 26

➝ Immunohistochemistry to check for mismatch repair genes in Lynch Syndrome

Question 27

What sequencing is done if someone has breast cancer?

Answer 27

➝ BRCA sequencing

Question 28

What are two syndromic features of having a cancer predisposition gene?

Answer 28

➝ mucocutaneous pigmentation | ➝ trichilemmoma

Question 29

What are the 4 decisions to make after assessment?

Answer 29

➝ Is there an increased inherited risk of cancer? ➝How high is the risk? ➝Does the patient need genetic testing to look for high risk cancer predisposition genes? ➝Does the patient and/or their relatives need extra screening or other measures to reduce cancer risk?

Question 30

How do you assess for inherited cancer risk?

Answer 30

➝ take 3 generational family history ➝ ages, types of cancer and number of affected relatives ➝ ethnic origin ➝ look for rare syndromic features ➝ use national genomic test directory eligibility to decide if genetic testing is indicated

Question 31

What is the chance of having a cancer predisposition gene if you have multifactorial/polygenic risk?

Answer 31

➝ <10% chance

Question 32

What is chemoprevention?

Answer 32

➝ taking medication to reduce cancer risk

Question 33

What are two examples of chemoprevention?

Answer 33

➝ breast cancer - taking tamoxifen or SERM | ➝ colorectal cancer - taking aspirin

Question 34

What are two considerations when testing for high risk cancer predisposition genes?

Answer 34

➝ Implications for the individuals Recurrence risks Risks of other cancer ➝ Implications for relatives How to share information Concerns about children Family planning options

Question 35

What is diagnostic testing for and who is it done on?

Answer 35

➝To confirm whether a cancer predisposition gene has caused the cancer ➝Done with a person with cancer

Question 36

What is predictive testing for?

Answer 36

➝To identify if an unaffected person carries a cancer predisposition gene ➝Insurance implications

Question 37

What are the three outcomes of testing?

Answer 37

➝ No genetic variant identified ➝No genetic variant identified ➝Disease causing variant in CPG identified

Question 38

What are the two things done after no genetic variant is identified in testing?

Answer 38

➝Screening and management on personal and family history | ➝Referral for screening/further management only if indicated on above assessment

Question 39

What is done after a variant of uncertain significance is found in testing?

Answer 39

➝Referral for screening/further management only if indicated on above assessment ➝May be anxiety provoking for patients ➝Benign until proven guilty

Question 40

What is done after a disease causing variant in a cancer predisposition gene is found?

Answer 40

➝ Screening and management tailored to specific CPG | ➝Should be reviewed by NHS clinical genetics service

Question 41

What are 4 differences between sporadic cancers and hereditary cancers?

Answer 41

``` Sporadic ➝ no increased risk of other cancers ➝ usually small risk to relatives ➝ no genetic testing indicated ➝ normal clinical management ``` Hereditary ➝ high risk of recurrence/associated cancers ➝ high cancer risk in relatives ➝ testing and screening and preventative measures offered ➝ different treatment

Question 42

What kinds of mutations do sporadic and inherited cancers have?

Answer 42

➝ sporadic - somatic mutation | ➝ hereditary - germline