Cancer genetics

Question 1

What are some factors that contribute to the changes/mutations that occur over time in genes that can lead to cancer?

Answer 1

Lifestyle things – smoking
Exposures – environmental, occupational
Internal factors – viruses, hormones

Question 2

What percentage of cancers are hereditary (attributed to the inheritance of a single gene)??

Answer 2

10%

Question 3

What percentage of cancer is considered familial (d/t multiple genes and environmental factors)?

Answer 3

30%

Question 4

Explain how retinoblastoma can be hereditary.

Answer 4

Mutation in on copy of RB gene inherited in all body cells (would see this in a genetic test of the blood); the 2nd mutation occurs to knock out tumor suppressor gene (would see this mutation if you test the tumor)

Question 5

Explain how retinoblastoma can be non-hereditary.

Answer 5

Fertilized egg inherits no RB mutation (would not see a mutation if you genetically tested the germ line); mutation in one copy of RB gene occurs as cells divide then a mutation in the second copy of RB gene occurs in one or more retina cells (2nd hit) – would find 2 acquired mutations if you test the tumor

Question 6

What are some of the “red flags” for families with hereditary cancer?

Answer 6

Younger than expected age of diagnosis (<50yo)
Many affected family members
More than one generation affected
Pairing of cancers in the family (br & ov, colon & endo)
More than one cancer in the same person
Ashkenazi Jewish heritage

Question 7

What are two common hereditary cancer syndromes we should know?

Answer 7

Hereditary Breast and Ovarian Cancer Syndrom

Hereditary Nonpolyposis Colorectal Cancer Syndrom (Lynch)

Question 8

What is GINA?

Answer 8

Genetic information nondiscrimination act – federal law passed in 2008 that protects individuals from genetic discrimination in health insurance and employment

Question 9

What are some examples of populations of women who are at high lifetime risk of breast cancer?

Answer 9

Have a known BRCA1 or BRCA2 gene mutation

Have a first degree relative with BRCA1 or BRCA2 gene mutations but has not had testing themselves

Question 10

Does a negative BRCA test mean someone will not get breast cancer??

Answer 10

NO – test results must always be interpreted in the context of personal and family history

Question 11

What is Lynch Syndrome?

Answer 11

Hereditary Non-polyposis Colon Cancer – have much higher risk for a lot of different types of cancer

Associated with pathogenic variants in the MLH1, MSH2, PMS2 or EPCAM genes.

Question 12

What is Costello Syndrome?

Answer 12

RASopathy
Increased risk of solid tumors (rhabdomyosarcoma, neuroblastoma, transitional cell carcinoma of the bladder)
Hypertrophic cardiomyopathy rare but reported
Developmental delay
Characteristic facial features

Question 13

What is cardiofaciocutaneous (CFC) syndrome??

Answer 13

RASopathy
No conclusive increased risk of malignancy (leukemia/lymphoma)
Congenital heart disease and hypertrophic cardiomyopathy common – can be progressive
Developmental delay, IQ can be normal
Characteristic facial features