Inherited breast cancer

Question 1

How much does a first-degree relative’s breast cancer diagnosis increase a woman’s risk of developing breast cancer?

Answer 1

Doubles the risk

Question 2

Which two genes are major contributors to inherited breast cancer?

Answer 2

BRCA1 and BRCA2

Question 3

What percentage of breast cancer cases are attributed to inherited mutations in BRCA1 or BRCA2?

Answer 3

Approximately 1% to 3%

Question 4

Among women with breast cancer and a positive family history, what percentage have inherited mutations in BRCA1 or BRCA2?

Answer 4

Approximately 20% to 30%

Question 5

What is the lifetime risk of developing breast cancer for women who inherit a BRCA1 mutation?

Answer 5

50% to 80%

Question 6

What is the lifetime risk of developing breast cancer for women who inherit a BRCA2 mutation?

Answer 6

Approximately 50%

Question 7

What is the lifetime risk of ovarian cancer for women with BRCA1 mutations?

Answer 7

40%–50%

Question 8

What is the lifetime risk of ovarian cancer for women with BRCA2 mutations?

Answer 8

20%

Question 9

How are BRCA1 and BRCA2 mutations typically identified?

Answer 9

Linkage analysis followed by positional cloning

Question 10

What model describes the inheritance pattern of BRCA1 and BRCA2 mutations?

Answer 10

Two-hit model for tumor suppressor genes

Question 11

What role does BRCA1 play in DNA repair?

Answer 11

Phosphorylated by ATM and CHEK2 in response to double-stranded DNA breaks

Question 12

What is the relationship between BRCA1 and RAD51?

Answer 12

BRCA1 binds to BRCA2, which interacts with RAD51 for DNA repair

Question 13

What is the risk increase of breast cancer among heterozygous carriers of ATM mutations?

Answer 13

Approximately double that of the general population

Question 14

What happens when p16 activity is lost?

Answer 14

Increased CDK4 and CDK6 activity leading to cell proliferation

Question 15

What type of mutations in CDKN2A are common in sporadic melanomas?

Answer 15

Somatic loss-of-function mutations

Question 16

What is the primary mutation leading to familial melanoma?

Answer 16

Loss-of-function mutations in CDKN2A

Question 17

What is the second most common cancer among men?

Answer 17

Prostate cancer

Question 18

How does a first-degree relative’s prostate cancer diagnosis affect a man’s risk?

Answer 18

Doubles the risk

Question 19

What increases the prostate cancer risk to fourfold?

Answer 19

A first-degree relative diagnosed before age 60 years

Question 20

What has been challenging about identifying major genes for prostate cancer?

Answer 20

Difficulty in finding germline mutations that significantly increase risk

Question 21

What is the impact of having a first-degree relative affected by prostate cancer?

Answer 21

A man’s risk for prostate cancer doubles if one first-degree relative is affected and increases to fourfold if diagnosed before age 60 years.

Question 22

What mutation is identified in linkage studies that causes early-onset prostate cancer?

Answer 22

Mutation in HOXB13.

Question 23

Which inherited variants significantly increase the risk of prostate cancer?

Answer 23

• BRCA1
• BRCA2
• CHEK2
• PALB2
• MSH2

Question 24

What is the RET proto-oncogene involved in?

Answer 24

Embryonic neural crest cell migration.

Question 25

What does the RET proto-oncogene encode?

Answer 25

A receptor tyrosine kinase.

Question 26

What can inherited loss-of-function mutations in RET produce?

Answer 26

Hirschsprung disease.

Question 27

What does the RET gene exemplify regarding mutations?

Answer 27

Extraordinary allelic heterogeneity.

Question 28

What type of mutations in RET lead to various forms of endocrine neoplasia?

Answer 28

Germline gain-of-function mutations.