Hereditary Cancer

Question 1

Cancer genetic counseling is indicated when?

Answer 1

• Cancer in 2 or more relatives
• Early onset (<50)
• Multiple primary tumors
• Bilateral cancer
• Characteristics of cancer family syndrome

Question 2

3 classes of cancer genes

Answer 2

1) Oncogenes- 1 mutation sufficient
2) Tumor supressor genes- 2 mutations leads to cancer.
3) DNA damage-response genes: When both genes fail

Question 3

BRCA1 is a tumor ________ gene on chromosome 17. It is __________ dominant transmission. Protein has role in genomic stability. ~500 different mutations reported.

Answer 3

Suppressor, autosomal

Question 4

What is a tumor suppressor gene on chromosome 13 that is autosomal dominant transmission. ~300 mutations reported.

Answer 4

BRCA2

Question 5

What population has an increased risk of carrying BRCA1 and BRCA2 mutations?

Answer 5

Ashkenazi Jewish population

Question 6

Familial adenomatous polyposis (FAP): Estimated _________ for adenoma >90%. Risk of extracolonic tumors. CHRPE may be _______. Untreated polyposis leads to 100% risk of cancer.

Answer 6

penetrance, present

Question 7

FAP is ______ dominant inheritence. Caused by mutations in ___ tumor suppressor gene on Ch. 5q.

Answer 7

Autosomal, APC

Question 8

A variant of FAP is called __________ syndrome. It features FAP plus extraintestinal lesions.

Answer 8

Gardner’s

Question 9

Explain attenuated FAP

Answer 9

• Later onset
• Fewer colonic adenomas
• Not associated with CHRPE
• UGI lesions
• Assoc with mutations at 5’ and 3’ ends of APC gene.

Question 10

HNPCC (Lynch Syndrome) is seen when? Where is tumor?

Answer 10

• Early but variable age at CRC diagnosis (45 yrs)

- In proximal colon predominates.

Question 11

HNPCC is _________ dominant inheritence. Penetrance is 80%. Genes belong to DNA _________ _________ family. Genetic hetrogeneity:

Answer 11

• Autosomal.
• Mismatch repair (MMR)
• MLH1, MSH2, MSH6, PMS1, PMS2

Question 12

Mismatch repair failure leads to what?

Answer 12

Microsatellite Instability (MSI)- present in >90% of HNPCC

Question 13

How would you manage Cancer risk of HNPCC?

Answer 13

Surveillance:
-Colonoscopy every 1-3 years beginning at 20-25, annually after 40.
-Annual transvaginal US and endometrial aspiration beginning at 25-35.
Surgery:
-Subtotal colectomy
-Hysterectomy/Salpingo-oophorectomy