Genetics - Predisposition to Cancer

Question 1

what % of DNA is entragenic and can therefore code for proteins

Answer 1

2%

Question 2

what is nonsense mediated decay of DNA?

Answer 2

premature stop codon resulting in a shorter protein than expected

Question 3

what % of breast ca is hereditary?

Answer 3

5-10%

Question 4

what % of ovarian ca is hereditary?

Answer 4

5-10%

Question 5

genes linked to breast ca

Answer 5

BRCA 1 + 2

P53

Question 6

germline mutations

Answer 6

o Present in egg or sperm
o Are heritable
o Cause cancer family syndromes

Question 7

somatic mutations in cancer

Answer 7

o Occur in nongermline tissues

o Are nonheritable

Question 8

oncogenes and cancer

Answer 8

1st mutation leads to accelerated cell division.
Leukemias – oncogene ABL, BCR-ABL fusion protein. This switches on the BCR which creates and oncogene causing increased cell division.

Question 9

tumour suppressor genes in cancer

Answer 9

When the first mutation happens, the person becomes susceptible to cancer but the 2nd loss or mutation leads to cancer.

Question 10

hereditary non-polyposis colon cancer/lynch syndrome

Answer 10

• Mutation in mismatch repair genes
• Excess of colorectal, endometrial, urinary tract, ovarian and gastric cancers
• Adenoma- carcinoma sequence for polyp formation
• Great opportunity for prevention by colonoscopy
• Early but variable age at CRC diagnosis (approx. 45)
• Tumour site in proximal colon predominat

Question 11

life time risk of cancer in BRCA 1 + 2 related cancers

Answer 11

o Breast cancer – 60-80% often at early age
o Second primary breast cancer 40-60%
o Ovarian cancer BRCA 1 50%, BRCA 2 20%
o Males have an increases risk of prostate cancer and breast cancer esp. BRCA2

Question 12

when to suspect hereditary cancer syndrome

Answer 12

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

Question 13

cancer genetics process

Answer 13

• Obtain detailed family Hx
Figure 8 Inheritance
• Confirm diagnoses of cancer
• Risk estimation
• Counselling

Question 14

clinical genetics consultation

Answer 14

• Go through family history
• Risk estimation
• Explanation of basis of risk
• Intervention
o Increased awareness of symptoms/signs
o Lifestyle – diet, smoking, oestrogen use
o Screening
o Prophylactic surgery
• Genetic testing – consider in high risk

Question 15

breast cancer surveillance syndromes

Answer 15

• Breast awareness
• Early clinical surveillance 5yr < age 1st Ca in cancer
o Annual or clinical breast exams
o Mammography
§ Moderate/high: 2 yearly from 35-40, yearly 40-50
§ High only 18 monthly 50 – 64
o MR screening those at highest risk

Question 16

prophylactic mastectomy for hereditary breast ca

Answer 16

• Removes most but not all breast tissue
• Significantly reduces breast cancer risk in woman with a family history
• Total (simple) mastectomy removes more breast tissue than SC mastectomy (leave nipples)
Figure 9 Always Double Check Family History
• BRCA1 positive women mastectomy reduces incidence to 5%

Question 17

prophylactic mastectomy for hereditary ovarian cancer

Answer 17

• Eliminates risk of primary ovarian cancer; however, peritoneal carcinomatosis may still occur
o Embryonic remnants
• Laparoscopic oophorectomy reduces postsurgical morbidity
• Induces surgical menopause but HRT till 50 does not change breast cancer risk (as body would
have had it anyway)
• Risk of subsequent breast Ca halved in mutation positive women

Question 18

surveillance for CRC

Answer 18

• Colorectal cancer
o Colonoscopy
o High risk 2 yearly from 25
o Moderate risk 35-55
• Endometrial
o Only for women with Lynch syndrome mutations
o Look for PMB
o Transvaginal USS
o Surgery
o Screening not recommended

Question 19

benefits of genetic testing

Answer 19

o Identifies highest risk
o Identifies non-carriers in families with a known mutation
o Allows early detection and prevention strategies
o May relieve anxiety

Question 20

risks and limitations of genetic testing

Answer 20

o Does not detect all mutations
o Continued risk of sporadic cancer
o Efficacy of interventions variable
o May result in psychosocial or economic harm