Cancer

Question 1

Cancer

Answer 1

Defective cellular proliferation
Defective cellular differentiation
- Malignant
less differentiated
Grow rapidly- lost ability to control cell proliferation and differentiation-> disorganised growth and metastasis (invade and infiltrate)
2 categories- solid tumours and hematologic

Question 2

Genetically altered cell

Answer 2

A cell within a normal population sustains genetic mutation that increases its propensity ti proliferate when it would normally rest.

Question 3

Hyperplasia

Answer 3

The altered cell and its dependent continue to look normal but they reproduce too much. After years one in a million of these cells suffers another mutation that further loosens controls on cell growth.

Question 4

Dysplasia

Answer 4

In addition to proliferating excessively these cells mutate which alters cell behaviour.

Question 5

Metastasis

Answer 5

Cells mutate the ability to Lyse and gain access to circulatory system giving them access to the rest of the body.

Question 6

Tumour cell characters

Answer 6

• Differentiation anaplasia
• Genetic instability and chromosome abnormality
• Growth
• Growth factor independence
• Lack of cell density inhibition
• Impaired cohesiveness and adhesion
• Anchorage independence
• Faulty cell-cell communication
• Immortality

Question 7

CANCER CLASSIFICATION - Grade

Answer 7

HISTOLOGY
Grade l: cell differ slightly from normal cells and well differentiated
Grade ll: cells are more abnormal and moderately differentiated
Grade lll: cells are very abnormal and poorly differentiated
Grade lV: cells are immature and undifferentiated

Question 8

CANCER CLASSIFICATION- Stage

Answer 8

EXTENT OF DISEASE:
Stage 0: cancer in situ
Stage l: tumour limited to the tissue of origin
Stage ll: limited local spread
Stage lll: extensive local and regional spread
Stage lV: metastasis

Question 9

Genetic and Molecular basis of CANCER

Answer 9

Recognition of genetic factors in cancers has important implications:
identifying individuals who are at particular risk;
BRCA1 and BRAC2 mutation
Present in 33% women under 29 with breast cancer
Present 2% women 70-79 with breast cancer
means for diagnosis,
Leads to the development of therapy
Molecular fingerprint.
Epigenetic factors and micro RNA genes
There are 2 key differences between cancer and most genetic diseases: -
most Cancer, caused by somatic mutations, all other genetic diseases caused by germline mutations.
Each cancer arises from the accumulation of several mutations - “multi-hit” process.

Question 10

Cell division and its control

Answer 10

p53 acts to activate the transcription of p21 and p27 inhibitors of the cdk/cyclin kinases and therefore work to block the transition of the cell from G1 to S.

Question 11

Mutations and cancer

Answer 11

Control of cell division is regulated in 2 ways:

1. Genes that suppress cell division -Tumour suppressor genes - control abnormal cell proliferation and therefore suppress tumorigenesis e.g. p53, RB1
2. Genes that promote cell division (proto-) Oncogenes promotes cell proliferation and differentiation, e.g. growth factors, transmembrane kinase, signal transducers

Question 12

Knudsons 2 hit hypothesis

Answer 12

Sporadic - takes time to inactivate both copies of the allele
Hereditary - one copy already inactivated so cancer develops much faster.

Question 13

STAGES OF CANCER DEVELOPMENT

Answer 13

INITIATION-irriversible alteration in the cell’s genetic structure
PROMOTION-second cell mutation
PROGRESSION-increased growth rate, invasiveness, cell proliferation and metastasis

Question 14

Environmental factors

Answer 14

Diet/lifestyle (eating, breathing, sex, sun, alcohol)
Tobacco
Viruses (HIV, HepB, HPV)
Occupational exposure

Question 15

ROLE OF IMMUNE SYSTEM

Answer 15

To detect microorganisms and dead cells.
To destroy microorganisms and dead cells.
Tumour-associated antigens make it possible for immune system to detect cancer and destroy it.
If tumour-associated antigens are altered the immune system may fail to detect cancer cells.
Blocking of antigen will prevent recognition by antibodies and therefore no destruction of cancer cells occurs.

Question 16

Breast Cancer

Answer 16

90% sporadic
Family aggregation
BRCA1 and BRCA2 constitute about 10% all breast cancers
BRCA1 Chr 17, AD predisposition
85% of people who carry one mutant BRCA1 develop second mutation and hence breast cancer, also have increased risk of ovarian cancer
BRCA2- breast cancer only, Chr13, AD predisposition
Also in men (100 lower lifetime risk)
Risk factors for breast cancer:
affected first degree relative (risk doubles )
BRCA1 and BRCA2
Li-Fraumeni syndrome
Environmental factors
Nulliparity
First child after 30
High fat diet
Alcohol use
Oestrogen replacement therapy

Question 17

Colon Cancer

Answer 17

Multistep
Complex interaction between somatic gene alterations and environmental factors
E.g. lack of physical activity, high fat low fibre diet
95% sporadic
Lifetime risk in UK 1 in 30
2 forms hereditary:
FAP (familial adenomatous polyposis) 1%
rapid tumour initiation, slow progression
HNPCC ( hereditary nonpolyposis colorectal cancer) 2-4%
slow initiation, rapid progression

Question 18

Colon cancer

Answer 18

• The most frequent mutation (~10%) is a 5bp deletion (AAAGA) at nucleotides 3927-3931.
• Subsequent mutation, e.g. in ras oncogene (chr 12) results in intermediate tumour formation where the polyp grows larger (late adenoma state).
• To progress further the polyp cell must acquire mutations in (or loss of ) DCC (chr 18) to form late stage adenomas.
• A p53 mutation then results in transition to a cancerous cell with the final stage being metastasis.

Question 19

SEVEN WARNING SIGNS OF CANCER

Answer 19

Change in bowel or bladder habits
A sore that does not heal
Unusual bleeding or discharge from any body orifice
Thickening or a lump in the breast or elsewhere
Indigestion or difficulty swallowing
Obvious change in a wart or mole
Nagging cough or horseness

Question 20

Biochemical impacts of cancer on the body

Answer 20

Include malnutrition, anorexia, malabsorption, cancer cachexia, fluid and electrolyte imbalances, fatigue and sleep disorder and pain.
Cancer cachexia = protein/energy malnutrition
Due to combination of
excessive demands of rapid growth of cancer cells for glucose –increased energy demands
Reduced energy intake& malnutrtion due to loss of appetite, altered taste - reduced food intake + reduced absorption
Death may occur due to cachexia linked starvation rather than the actual cancer
Importance of early active nutritional intervention to attempt to reduce this- with kilojoules and protein – small frequent appealing, easy to digest meals rather than bulky low energy dense high fibre foods!
Unexplained weight loss needs to be checked-
May mean an undiagnosed cancer

Question 21

CANCER- screening

Answer 21

1. Cytology e.g. Pap smear, biopsy, bone marrow
   2.Radiography - Chest X-ray, CT (computer tomography) scan, MRI (magnetic resonance imaging), mammogram
   3.Indirect non-specific tests e.g. liver function, abnormal hormones, blood count , blood in stools, sudden unexplained weight loss, etc
   4.Tumor markers- e.g. PAP, PSA for cancer of the prostrate, CA125 for ovarian cancer.
   But note – these are not completely accurate- need to be confirmed, or done regularly when a sudden increase may indicate a need for a further check up

Question 22

CANCER TREATMENT

Answer 22

Avoidance
 Environmental exposure
 Screening
 Smear, mammography, gene screen,
protein profile
 CHEMOTHERAPY
 Targets rapidly dividing cells
 RADIOTHERAPY
 generates DNA strand breaks through
free radical formation: provided the
damage is extensive, the cell dies by the
apoptopic pathway. Repeated low dose.
 SURGERY
 Excellent provided no metastasis and detected
early enough, could trigger metastasis?

Question 23

CANCER – summing it up

Answer 23

Cancer is the second leading cause of deaths in New
Zealand
 Main cancers in NZ affect the lung, colon, breast,
prostate and melanoma
 Risk factors for cancer include smoking, diet,
environment and occupations with carcinogens playing a
major role.
 Diet - cancer promoting- or cancer protective
 Other predisposing factors include genetics (oncogenes
etc) and stress, lack of physical activity