Genetic Predispodition to Cancer

Question 1

does intragenic or extragenic DNA have strong cancer predisposition?

Answer 1

intragenic

Question 2

what is a germline mutation?

Answer 2

a mutation in the sperm/egg causing family cancer syndromes

Question 3

true or false

in germline mutations all cells are affected in the offspring

Answer 3

true

Question 4

describe somatic mutations

Answer 4

these occur in non-germline tissues and are non-heritable

Question 5

a child has a retinoblastoma and a germline mutation. what are they are risk of?

Answer 5

cancer in the other eye

Question 6

a mutation in an oncogene can lead to what?

Answer 6

accelerated cell division leading to cancer growth

Question 7

what are tumour suppressor genes?

Answer 7

normal genes that prevent cancer

Question 8

what are oncogenes?

Answer 8

normal genes that regulate cell growth

Question 9

describe DNA mismatch repair and how it could lead to cancer

Answer 9

so there is a base pair mismatch in the DNA which should normally be repaired but if it isn’t then a mutation in induced.

Question 10

describe inheritability of autosomal dominant condition

Answer 10

> each child has a 50% chance of inheriting it
there are no skipped generations
equally transmitted by men and women

Question 11

when should you suspect inheritance?

Answer 11

> 2 or more close relatives
> multiple primary tumours
> early age of diagnosis
> bilateral/multiple rare cancers
> evidence of autosomal dominant transmission
> characteristic pattern of tumours

Question 12

what intervention could be offered in a heritable cancer?

Answer 12

> counselling
increase awareness of symptoms and signs and lifestyle
screening
prophylactic surgery

Question 13

what are the risks and limitations of genetic testing?

Answer 13

> there is a continued risk of sporadic cancer
does not detect all mutations
efficacy of interventions are variable
may result in psychological or economic harm

Question 14

what are the benefits of genetic testing?

Answer 14

> identifies highest risk
identifies non-carriers
may relieve some anxiety
allows early detection and prevention strategies

Question 15

what mutation is present in hereditary non-polyposis colon cancer?

Answer 15

mutation in the mismatch repair genes

Question 16

what are the effects of HNPCC mutation?

Answer 16

> excessive colorectal, endometrial, urinary tract, ovarian and gastric cancer
adenoma-carcinoma sequence for polyp formation
early (but variable) age at CRC diagnosis
tumours in proximal colon predominates

Question 17

what surveillance is offered in HNPCC mutation?

Answer 17

colonoscopy
> high risk 2yrs from 25
> moderate risk 35yrs and 55yrs

post menopausal bleeding
transvaginal US
surgery

Question 18

what are the effects of BRAC 1 and 2?

Answer 18

> breast cancer: 60-80%
second primary breast cancer: 40-60%
ovarian cancer: 20%-50%
males: increased risk of prostate cancer and breast cancer (BRAC2)

Question 19

what surveillance is carried out in BRAC 1/2?

Answer 19

Breast
> awareness
> early clinical surveillance 5yrs before age of first onset of cancer in the family
> mammography: 2yrs from 35/40, yearly 40/50 (18 monthly 50-64 if high risk)
> prophylactic mastectomy

Prophylactic oophorectomy
> induces surgical menopause but HRT till 50 has no cancer risk
> halves risk in +ve women