Genetic Predisposition to Cancer

Question 1

Somatic mutations

Answer 1

These are acquired and are non-germline so non-inheritable therefore leading to sporadic cancer.

Question 2

Germline mutations

Answer 2

Occur in egg/sperm so are inheritable (5-10% of all cancers)

Question 3

Oncogenes

Answer 3

Oncogenes are formed by mutations in proto-oncogenes which code for proteins regulating cell growth and differentiation. They accelerate cell division causing cancer when stuck in the on position.

Question 4

Tumour suppressor genes

Answer 4

These act as brakes for cell growth. Genes also inhibit cell cycle/promote apoptosis. Cancer arises when both brakes fail.

Question 5

Two hit hypothesis

Answer 5

E.g first hit is a susceptible carrier in germline of child then second hit is a mutation or loss leading to a tumour.

Question 6

DNA damage-response genes

Answer 6

The repair mechanics for DNA. Cancer arises when both genes fail, speeding up the accumulation of mutations in other critical genes.

Question 7

Other mechanisms of inherited predisposition to cancer

Answer 7

Autosomal recessive syndromes, multiple modifier genes of lower genetic risk, De Novo (new) mutations.

Question 8

Look for…

Answer 8

Family history, mutation testing, regular surveillance , exome and genome sequencing.

Question 9

Environmental risk factors

Answer 9

Family history, early menarche (menstruation), late menopause, ageing, nulliparity, oestrogen use, diet, lack of exercise.