Unit 2: Cancer risk factors (diet and lifestyle)

Question 1

What is meant by latency

Answer 1

The period of time between the initial genetic mutation and the clinical appearence of cancer e.g in chimney sweeps and scrotum cancer

Question 2

What is the hypothesis for the multistage model of carcinogenesis

Answer 2

Cancer results from the ACCUMULATION of mutations in growth-regulatory genes.

Question 3

What are the 3 phases of the multistep model of carcinogenesis

Answer 3

1. initiation = irriversible phase where genetic mutation
   occurs in a target cell
2. promotion = exposure to a stimulatory agent
   causes clonal expansion of mutated cell
3. Progression = Further genetic alterations which
   support tumour progression and aggressivness

Question 4

What genetic mutations occur in the irriversible initiation stage.

Answer 4

• Activation of proto-oncogenes –> oncogenes
• Inactivation of tumour supressors
  These initiating mutations are passed on to daughter
  cells if unrepaired and CONTAIN A GROWTH
  ADVANTAGE

Question 5

What type of carcinogens are involved in the promotion stage and is this reversible?

Answer 5

Mitogens (promote growth) can drive tumour promotion. However this can be reversible at an early stage.

Question 6

Outline the progression phase and is this reversible

Answer 6

Tumours accumulate further mutations which enable further growth and aggressive features and again in cancer hallmarks. This is now irriversible.

Question 7

Who came up with the multistage model of carcinogenesis and what cancer did he use to demonstrate this?

Answer 7

Vogelstein used colorectal cancer to describe the accumulation of genes.

Question 8

Outline Vogelsteins cholorectal model of multistage carcinogenesis

Answer 8

1. Loss mutation in APC (Adenomatous polyposis coli)
2. causes hyperproliferion of endothelium in colonic
   mucosa.
3. KRAS mutations gained which promote
   hyperproliferating endothelium to adenoma
4. Further mutations in TF’s and p53 gives rise to
   adenocarcinoma (cancerous).
5. Further mutations enable aggressive and metastatic
   carcinoma

Question 9

What % of lung cancer is attributed to smoking

Answer 9

90%

Question 10

Why does smoking lead to cancer

Answer 10

Tobacco smoke contains >5,000 chemicals of which 60 are carcinogenic. These contribute to the initiation event of cancer by causing permenant DNA adducts.

Question 11

What are intrinsic risk factors

Answer 11

Age, race, familial history, inherited syndromes

Question 12

What are extrinsic factors

Answer 12

Diet, physical activity, obesity, smoking (lifestyle CHOICES)

Question 13

At what geographical location is cholorectal cancer the highest and why?

Answer 13

USA due to highest calorific intake

Question 14

Why does excess dietry protein contribute to cholorectal cancer

Answer 14

Undigested proteins are broken down by bacteria in gut which produces ammonia, phenols, HS.
These are absorbed (mainly ammonia) by the cholonocytes which increases luminal pH & O2 and increases inflamation & proliferation.

Question 15

Why does processed meat contribute to cholorectal cancer

Answer 15

Presence of nitrate, nitrite and nitrosamines in processed foods which cause local inflamation and mucousal damage when broken down to produce N-nitroso compounds (NOC) which form DNA adducts.

Question 16

Why does a high fat diet contribute to cholorectal cancer

Answer 16

Animal fats increase bile acid in the colon which, when degraded by bacteria forms deoxcycholic acid which increases proliferation of cholonocytes, increases ROS and increases local inflamation.

Question 17

Why do breakdown products of digestion effect cholonocytes so much?

Answer 17

Cholonocytes try to adapt to their toxic environment of waste products (e.g ROS, NOC’s, ammonia) and therefore absorb these. This then cause DNA damage/adducts within the cholonocytes.