Clinical Cancer Genetics

Question 1

What can we do to reduce cancer risk in people at increased genetic risk

Answer 1

Screening
Prevention
Early Detection

Question 2

DNA - define

Answer 2

A molecule which contains the human genetic code

Question 3

Genes - define

Answer 3

The instructions to tell the body how to grow, develop and function

Consist of sections of DNA which the cell translates into proteins
~ 20,000 genes in the human genome

2 copies of most genes – one on each chromosome

Question 4

The human genome - define

Answer 4

The human genome
The entire length of DNA contained in human cells
3 billion bases

Question 5

Explain importance of genetic variation

Answer 5

We have around 5 million different genetic changes compared to another unrelated person

Genetic variation makes us unique

Genetic variation may influence our chance of developing disease

Question 6

Sporadic cancers - define

Answer 6

Most cancers are “sporadic” – due to acquired (somatic) mutations within a cell
giving it a growth advantage

Acquired mutations in cancer genes “drive” the cell to become cancerous
Not inherited changes

Question 7

Explain risk of genetics in cancer - high/low

Answer 7

High risk cancer predisposition genes are rare

Low risk genetic changes increasing cancer risk are more common

Question 8

Describe cancers occur due to inherited genetic changes

Answer 8

A smaller proportion of cancers occur due to inherited genetic changes

These can be multiple lower risk genetic variants – this is known as multifactorial or polygenic risk

Or a single high risk genetic variant in a cancer predisposition gene

Question 9

Testing of the cancer - describe 2 parts

Answer 9

Pathology: certain pathological subtypes of cancers increase risk of high risk CPGs

Molecular testing: Tumour testing may identify genetic changes which could indicate inherited risk – need to check with a blood test

Question 10

List 2 syndromic features - cancer

Answer 10

trichilemmoma

Mucocutaneous pigmentation

Question 11

Decisions to make on assessment of cancer

Answer 11

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?
- Usually around a 1 in 10 chance of finding a mutation in a high risk cancer predisposition gene

Does the patient and/or their relatives need extra screening or other measures to reduce cancer risk?

Question 12

How do we decide if genetic testing is indicated in cancer

Answer 12

Use the National Genomic Test Directory Eligibility Criteria to decide if genetic testing is indicated

Question 13

Management of inherited cancer risk - method types

Answer 13

Offer screening, prevention and early detection advice (SPED)

Question 14

Management of inherited cancer risk - Implications for individual

Answer 14

Recurrence risks

Risks of other cancers

Question 15

Management of inherited cancer risk - Implications for relatives

Answer 15

How to share information
Concerns about children
Family planning options (e.g. prenatal, PGD)

Question 16

Diagnostic versus predictive testing

Answer 16

`Diagnostic testing:

To confirm whether a CPG has caused the cancer

Predictive testing:

To identify if an unaffected person carries a CPG

Insurance implications
- Current moratorium for predictive testing

Question 17

Outcomes of testing if no genetic variant identified

Answer 17

No genetic variant identified:

Screening and management on personal and family history
Referral for screening/further management only if indicated on above assessment
Reassuring for patient but reiterate participation in population screening programmes

Question 18

Outcomes of testing if disease causing variant in CPG identified

Answer 18

Screening and management tailored to specific CPG

Should be reviewed by NHS clinical genetics service

Question 19

Outcomes of testing if variant of uncertain significance (VUS) identified

Answer 19

Benign until proven guilty
Referral for screening/further management only if indicated on above assessment
May be anxiety provoking for patient. Need to understand how common genetic variation is and that most VUS are benign

Question 20

Hereditary cancers - characteristics

Answer 20

High risks of recurrence/other associated cancers
High cancer risks in relatives
We can offer testing to at risk individuals
We can offer screening and preventative management to gene carriers
May alter treatment of affected individuals

Question 21

Sporadic cancers - characteristics

Answer 21

No increased risk of other cancers
Usually small increased risk to relatives
No genetic testing indicated
Normal clinical management for affected individuals

Question 22

Germline vs somatic mutation

Answer 22

G = entire OG carries mutation
Present in sperm
Can be inherited
Cause cancer family syndrome
Half of gametes carry mutation 

S = patch of affected area
Occur in nongermline tissues
Cannot be inherited
S = non of gametes carry mutation