Inherited Diseases and Genes

Question 1

Define polymorphism?

Answer 1

Conservative changes which gives arise to alleles

Question 2

Define variation of unknown significance?

Answer 2

A change in the normal sequence of a gene where the clinical significance or the association with a disease is not known

Question 3

Name the four ways of gene transmission?

Answer 3

Autosomal dominant
Autosomal recessive
X-linked
Mitochondrial (non mandalian)

Question 4

Define penetrance?

Answer 4

The proportion of people with a gene mutation that will manifest the disease
i.e BRCA 1 penetrance = 30% of the people with the mutation manifest the disease

Question 5

Define expression?

Answer 5

How the gene mutation disease manifests itself

i.e BRCA 1 expression can either be breast cancer or ovarian cancer

Question 6

Describe the role of BRCA 1 and 2 genes?

Answer 6

Tumour suppressor gene works for double stranded DNA repair. It recruits other proteins (ATM/CHK.2) which works as DNA repair sensing proteins. If faulty genes are detected - the cell cycle is halted and DNA damage can be attempted to be repaired.

Question 7

Which cancers do harmful gene mutations in BRCA 1 and 2 increase the likelihood of?

Answer 7

Breast
Ovarian
Pancreas
Colon
Prostate

Question 8

Name seven risk factors associated with breast cancer?

Answer 8

Increasing age
Fhx
Female
Nulliparity
Late menopause
Early menarche
Not breastfeeding

Question 9

Name the six types of breast cancer?

Answer 9

Non-invasive ductal carcinoma in situ (premalignant)
Non-invasive lobular carcinoma in situ (multifocal)
Invasive ductal carcinoma (70%)
Invasive lobular carcinoma (15%)
Medullary carcinoma - young
Colloid/mucoid carcinoma - elderly

Question 10

What feature do 30% of cancers have that may make them more aggressive?

Answer 10

Her.2 positive

Question 11

What percentage of carcinomas are oestrogen receptor positive and what does this signify?

Answer 11

70%

Signifies a better prognosis

Question 12

Describe the triple assessment offered to women with a suspected breast lump?

Answer 12

1. Clinical Hx and O/E
2. Mammogram (only offered to women over 40)
3. Ultrasound
4. FNA (good at providing a rapid diagnosis of malignancy however core biopsy often effectively differentiates between pre-invasive and invasive disease)

Question 13

What endocrine agents are used if the pt with breast cancer is oestrogen/progesterone receptor positive and what are its side-effects?

Answer 13

Tamoxifen

S/E = Uterine cancer and vaginal bleeding?

Question 14

What endocrine agents are used if the pt with breast cancer is Her.2 receptor positive?

Answer 14

Herceptin (Trastuzumab)

Question 15

Define ‘diagnostic test’ in relation to breast cancer?

Answer 15

Blood taken from already diagnosed pt with breast cancer and checked for altered genes

Question 16

Define ‘predictive test’ in relation to breast cancer?

Answer 16

If altered gene is found from a diagnostic test then a predictive test becomes available for family members. If (+ve) it means that the you also have the faulty gene however it does NOT necessarily mean that you will go on to develop breast cancer. You have a 50% chance of passing on the condition to your children