Genes and Cancer 2

Question 1

Indicators of familial cancer

Answer 1

1. Involvement of close relatives – at least one first degree relative
2. Presence of cancer over successive generations
3. Young age at onset of cancer (for that type of cancer)
4. Multiple types of cancers – in same individual or within the family

Question 2

4 main genes involved in cancer formation

Answer 2

Oncogenes
Tumour suppressor genes
Genes involved in apoptosis
DNA repair genes

Question 3

Example of Oncogenes
- RET Oncogene

Answer 3

Germline mutations associated with MEN type 2 and familial medullary thyroid cancer

Lecture Slide

Question 4

Familial vs sporadic cancer progress

Answer 4

Lecture Slide

Question 5

Examples of familial cancer and their assosciated gene

Answer 5

Breast/ovary - BRCA1 and BCRA2

Colorectal -hMLH1, hMSH2

Question 6

Diagnosis of
HNPCC / Familial Colorectal cancer Process

Answer 6

1. Clinical suspicion
   Eg young age at diagnosis, other family members with cancer, Amsterdam Criteria
2. Further analysis of the cancer tissue
   Microsatellite instability in the tumour
   Immunohistochemistry to detect expression of mismatch repair gene
3. Genetic studies looking for germline mutation of a
   mismatch repair gene

Question 7

Management
of families with HNPCC

Answer 7

Regular screening by colonoscopy

Question 8

Familial Adenomatous Polyposis

Answer 8

Autosomal dominant disorder with multiple
polyps or adenomas in bowel – transform to carcinomas

Polyps begin to develop second decade of life - 12years need colonoscopy.

Question 9

Genetics of Familial Adenomatous Polyposis

Answer 9

5q – APC gene mutation

Inherited germline mutation
Most mutations frameshift or nonsense – yield truncated protein
Second hit required – sometimes hypomethylation

Question 10

Function of BRCA 1 and 2

Answer 10

Protein products involved in DNA repair

Question 11

Clinical reasoning to assume familial breast cancer

Answer 11

1. Clinical suspicion
   Family history, breast and ovarian cancer
2. Analysis of the tumour
   Similar features to sporadic breast cancer
3. BRCA gene analysis for germline mutation

Question 12

For men, what does BRCA 1 and 2 mutations increase the risk of ?

For WOMEN, what does BRCA 1 and 2 mutations increase the risk of ?

Answer 12

prostate cancer and breast cancer

Breast and ovarian cancer