Genetics - Predisposition To Cancer

Question 1

Germline mutations

Answer 1

• inherited from single alteration in egg or sperm
• are heritable
• cause cancer family syndromes

Question 2

Somatic mutations

Answer 2

• occur in non germ line tissues

- are nonheritable

Question 3

BRCA1 and 2 Associated Cancers: Lifetime Risk

Answer 3

• Breast cancer 60%-80% (often early age at onset)
• Second primary breast cancer 40%-60%
• Ovarian cancer 20%-50%
• Males: increased risk of prostate cancer and breast cancer esp. BRCA2

Question 4

When to Suspect

Hereditary Cancer Syndrome

Answer 4

• Cancer in 2 or more close relatives (on same side of family)
• Early age at diagnosis
• Multiple primary tumors
• Bilateral or multiple rare cancers
• Characteristic pattern of tumours (e.g. breast and ovary)
• Evidence of autosomal dominant transmission

Question 5

Clinical Genetics Consultation

Answer 5

• Go through family history
• Risk estimation
• Explanation of basis of risk
• Interventions
  - increased awareness of symptoms / signs
  - lifestyle - diet, smoking, exercise,
  - Prevention – oestrogen, aspirin use
  - screening
  - prophylactic surgery
• Genetic testing - consider in high risk

Question 6

Breast Cancer Surveillance Options

Answer 6

• Breast awareness

- Early clinical surveillance 5 yr

Question 7

BRCA1/2 Gene Carriers:

Prophylactic Mastectomy

Answer 7

• Removes most but not all breast tissue
• Significantly reduces breast cancer risk in women with a family history
• Total (simple) mastectomy removes more breast tissue than subcutaneous mastectomy
• BRCA1 mutation-positive women breast cancer incidence reduced to 5%

Question 8

Prophylactic Oophorectomy

Answer 8

-Eliminates risk of primary ovarian cancer;
however, peritoneal carcinomatosis may
still occur
-Laparoscopic oophorectomy reduces postsurgical morbidity
-Induces surgical menopause but HRT till 50 does not change BRCA risk
-Risk of subsequent BRCA halved in mutation-positive women

Question 9

Benefits of Genetic Testing

Answer 9

• identifies highest risk
• identifies non-carriers in families with a known mutation
• allows early detection and prevention strategies

Question 10

Risks, and Limitations of Genetic Testing

Answer 10

• does not detect all mutations
• continued risk of sporadic cancer
• efficacy of interventions is variable
• may result in psychological or economic harm