Basic Cancer Genetics

Question 1

Inheritance of heretidary cancers

Answer 1

Autosomal dominant (Nearly all)

Question 2

If one has young age of presentation + unusual combinations of cancers >>> What can be suspected?

Answer 2

Heritable cancer predisposing syndrome

Question 3

How is the penetrance in hereditary cancers?

Answer 3

Reduced

Question 4

Example of reduced penetrance in some cancers

Answer 4

80% risk of breast cancer in female carriers of BRCA1 & BRCA2 mutations

80% (males) & 60% (females) risk of colorectal cancer in case of HNPCC

50% risk of endometrial cancer in female HNPCC mutation carriers

Question 5

What other group of factors is important for cancer risk?

Answer 5

Life style factors

(They are even important for genetically high risk families)

Question 6

Lifestyle factors for bowel cancer

Answer 6

Smoking

Diet (fresh fruit, vegetables)

In particular, resistant starch

Weight maintenance

Question 7

Factors of breast cancer

Answer 7

Protective hormonal factors:

• Late age of menarche
• Early age at birth of first baby
• Breastfeeding for more than 6months
• Earlier menopause

Risk factors:

• Overweight
• COCP
• HRT

Question 8

What is Gorlin syndrome?

Answer 8

Basal cell naevus syndrome > predisposes to >>> skin cancers

Question 9

If a person has Gorlin syndrome or other conditions that predisposes to skin cancer, how to protect?

Answer 9

Meticulous sun protection

Avoidance of X-ray irradiation

Question 10

‘Certain tumours are unusual enough to be almost pathognomic for a certain syndrome’ >> such as?

Answer 10

Transitional cell carcinoma of the renal pelvis

Sebaceous tumours

Question 11

Transitional cell carcinoma of renal pelvis is pathognomic of >>??

Answer 11

HNPCC (Hereditary non-polyposis colorectal cancer)

Question 12

Sebaceous tumour is pathognomic of >> ?

Answer 12

Muir Torre syndrome

Question 13

What is Muir Torre syndrome?

Answer 13

HNPCC + skin tumours (keratoacanthomas & sebaceous tumours)

Question 14

In which cancers, at-risk individuals need to be screened?

Answer 14

HNPCC

Hereditary breast and ovarian cancer

Von-Hippel-Lindau disease

Familial renal carcinomas

Question 15

Screening of HNPCC

Answer 15

In those who are proven mutation carriers OR those who have 50% risk

• ​Colonoscopy every 18-24 months​

(It varies for other diseases)

Question 16

Screening of high-risk hereditary breast and ovarian cancer

Answer 16

Mammography

where possible, MRI breast

(benefits of ovarian screening are not proven)

Question 17

Screening of Von Hippel Lindau disease

Answer 17

Annual renal ultrasound

Urinary catecholamines

Ophthalmic review

MRI brain & spine 2-3yearly

Question 18

In which cancers, prophylactic treatment can be given?

Answer 18

FAP (Familial Adenomatous Polyposis)

Hereditary breast and ovarian cancer

Question 19

Prophylactic treatment of FAP

Answer 19

Colectomy between 16 to 30years of age

Question 20

Why is prophylactic colectomy often performed in FAP (Familial Adenomatous Polyposis)?

Answer 20

Because development of malignancy is almost inevitable

Question 21

Why is prophylactic colectomy NOT performed in HNPCC?

Answer 21

Because, colonoscopy screening + polypectomy successfully prevent cancer

Question 22

In patients who are at high risk of hereditary breast and ovarian cancer, what are the prophylactic treatments?

Answer 22

Prophylactic mastectomy

Prophylactic oophorectomy

Prophylactic chemorpevention

Question 23

What is needed before prophylactic mastectomy/oophorectomy?

Answer 23

Aprropriate counselling

Question 24

In patients who are at high risk of hereditary breast and ovarian cancer, what is the effect of oophorectomy?

Answer 24

Oophorectomy reduces the risk of breast cancer and ovarian cancer both

Question 25

In patients who are at high risk of hereditary breast cancer, which chemical is used for prophylactic chemoprevention?

Answer 25

Tamoxifen

(Chemoprevention is only for certain sub-groups of women)