Genetic predisposition to cancer

Question 1

Lifetime Risk of ca with BRCA 1

Answer 1

Ovarian Ca 63% usually high-grade serous tumours
Breast Ca 85%
Latest %:
Ovarian Ca 39%
Breast Ca 65%

Question 2

Lifetime risk of ca with BRCA 2

Answer 2

Ovarian Ca 27% 
Breast Ca 84%
Latest %:
Ovarian Ca 11%
Breast Ca 45%

Question 3

Diagnostic genetic test

Answer 3

Full screen of the gene,normally undertaken in an individual affected with cancer

Question 4

Predictive genetic test

Answer 4

Targeted test for a specific mutation, previously identified in another family member, and usually undertaken in an individual who has not had cancer
(carrier probability of 10% or more)

Question 5

Proposed Patient selection for testing for BRCA 1 &2

Answer 5

Every woman with epithelial ovarian, fallopian tube and primary peritoneal carcinoma should be offered BRCA1 and BRCA2 gene testing, regardless of family history

Question 6

Risk reducing surgery

Answer 6

• Bilateral salpingo-oophorectomy (RRBSO) and risk-reducing breast surgery or breast screening
• 80 % decrease in ovarian cancer risk and 56% decreased risk in breast Ca
  and BRCA2 mutation carriers who underwent RRBSO.
• Residual 1–6% risk of primary peritoneal cancer that appears to persist for up to 20 years after oophorectomy
• 35-40 years appropriate to consider surgery BRCA 1
• 45 BRCA 2

Question 7

Lynch syndrome

Answer 7

• Germline mutations in the DNA mismatch repair (MMR) genes (MSH2,MLH1, MSH6, PMS2)
• Increased risk of early-onset cancer of multiple types,
  including colorectal, endometrial, ovarian, gastric, small bowel, hepatobiliary, brain, ureteric and renal
  pelvic cancers
• The lifetime risk for endometrial cancer is 40–60%
• the lifetime risk of ovarian carcinoma is 10–12%
• Often early stage and moderately or well differentiated
• Aspirin may reduce the risk of cancer after 5 years of use

Question 8

Cowden syndrome

Answer 8

• Cancer predisposition syndrome characterised by macrocephaly, multiple hamartomas and an increased risk of several tumour types, in particular breast, thyroid and endometrial cancers, but also colorectal, melanoma
  and renal cell carcinoma.
• Lifetime risk of endometrial cancer approaches 30%
• Germline mutations in the tumour suppressor gene PTEN cause PTEN hamartoma tumour syndrome
  (PHTS)

Question 9

Peutz-Jeghers syndrome

Answer 9

• Germline mutations in the STK11 gene
• autosomal dominant gastrointestinal polyposis disorder which confers an increased risk of breast, gastrointestinal and gynaecological tumours
• Characteristic pigmented lesions on the
  lips and buccal mucosa
• Risk of developing sex cord stromal tumours with annular tubules of the ovary and adenoma malignum of the cervix

Question 10

Li-Fraumeni syndrome

Answer 10

• Caused by germline TP53 mutations
• Cardinal features of the condition are young-onset sarcomas, breast cancer, adrenocortical carcinoma and childhood tumours.
• Most commonly diagnosed being epithelial ovarian
  carcinoma
• No definitive screening recommendations.