Cancer as as Preventable Disease

Question 1

Lung Cancer as preventable cancer?

Answer 1

Lifestyle factors:

Tobacco
= tobacco use causes 22% of all cancer deaths
= tobacco smoke causes DNA damage
= can be direct:
(e.g. polycyclic aromatic hydrocarbons bind to DNA and cause structural changes = mutations)
(e.g. benzene)
= can be indirect:
(generates reactive oxygen species and free radicals)
= if DNA not repaired, errors in replication, further mutations
= also will suppress immune system

Obesity / inactivity
= females more than males
= more in developed world
adipocytes:
= release adipokines = drive cell proliferation
= release oestrogen = drive growth of hormone responsive cells
= disrupt insulin signalling
= recruit macrophages = chronic inflammation

Question 2

Example of where prevention has worked?

Answer 2

= Malignant Melanoma

Global distribution:
= incidence increasing
= e.g. in Aus + Nz = thin ozone
= e.g. in europe = increased sunbeds and tanning

Lifestyle factors:
= sun exposure

Prevention Strategies:

Education
= Just eat more = 5 a day
= Slip slap slop = worked in Aus
= Shock Tactics

= shown to decrease incidence rates

Question 3

What are examples of Vaccination being used?

Answer 3

For when infectious agents are involved
= chronic infections cause 20% of all cancers
= affect developing world more

Vaccines in use:

HPV
= Gardasil (HPV6,11,16,18)
= Gardasil 9 (also adds HPV 31,33,45,52,59)
= Cervarix HPV (HPV 16,18)
= shown to decrease cervical cancer)

HBV
= Energix-B
= Recombivax HB

Vaccines in development
= EBV
= HCV
= H. pylori

Question 4

What are some known risk factors of liver cancer?

Answer 4

= multifactorial
= also known as Hepatocellular carcinoma

HBV
= causes 50% of liver cases
= liver damage through chronic inflammation (lymphocyte infiltration)

HCV
= causes 15% of liver cases
= liver damage through chronic inflammation (lymphocyte infiltration)

Aflatoxin contamination of food
= causes up to 28% of liver cases
= mycotoxin produced by Aspergillus spp. of fungi
= activated in liver, reacts with DNA
= very mutagenic + carcinogenic

Alcohol abuse
= via alcoholic fatty liver disease
= can progress to inflammtory state - steatohepatitis

Overweight / Obesity
= e.g. non-alochol fatty liver disease
= can progress to inflammtory state - steatohepatitis

Question 5

What is the progression of liver cancer (/Hepatocellular carcinoma) ?

Answer 5

80-90% of cases associated with cirrhosis
(chronic damage + inflammation)

1. Initiation
   = genetic changes in liver cells (due to the known risk factors e.g. HBV/HCV, alcohol)
2. Promotion
   = of cell growth and division
   = often driven by inflammation
3. Progression
   = cells may cause small clusters or nodules = become larger = forming tumour
   = get extensive collagen scarring = cirrhosis
4. Metastais
   = advanced stage can spread

Question 6

How to prevent liver cancer? + examples for other cancers?

Answer 6

Reducing HBV / HCV infection rates
= HBV vaccination (e.g. immunisation in Taiwan)
= elimiation of HCV iatrogenic sources (e.g. contaminated blood) (Seen in post-tranfusion hepatitis in Japan)

Education
= discourage sharing of needles by IDUs
= food storage / changes in diet
= reduce alcohol intake

Chemoprevention
e.g. target oestrogen signalling for prevention of breast cancer in high risk patients
= selective oestrogen receptor modulators - SERMs
(e.g. tamoxifen, raloxifene)
= aromatase inhibitors
(e.g. exemestane, letrozole)

EXTRA READING
= another chemoprevention= NSAIDS and prevention of colorectal cancer
= they inhibit enzyme COX - cyclooxygenase (involved in production of prostaglandins - role in inflammation, cell growth and survival)
= inhibition helps prevent growth of precancerous polyps and risk of colorectal cancer
= can induce apoptosis in cancer cells
= BUT risks such as GI bleeding and kidney damage

Question 7

What is the link between Oestrogen and breast cancer?

Answer 7

75% of breast cancers
= positive for oestrogen receptor

Strong link between oestrogen levels and breast cancer risk
= e.g. early menopause = 90% decreased risk
= e.g. post menopausal breast cancer patients = have 15% higher oestrogen levels

Oestrogen receptor + Oestradiol = recruits co-activator in cell = drives transcription

Question 8

What are examples of treatments targeting oestrogen for breast cancer? (+side-effects)

Answer 8

Aromatase inhibitors
= prevent oestrogen synthesis in peripheral fat
= decreases oestrogen levels in the body

= NO transcription of ER target genes
= menopausal symptoms, joint pain, osteoporosis

SERMs
= act as ER antagonists in breast tissue (target receptor)
= stops activation of target genes

= can act as ER AGONISTS in other tissues such as bone / endometrium
= increased risk of stroke / endometrium
= more severe side-effects
= BUT maybe more effective (50% reduction in breast cancer with tamoxifen for high risk patients)