Cancer Flashcards
Cancer
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
Genetically altered cell
A cell within a normal population sustains genetic mutation that increases its propensity ti proliferate when it would normally rest.
Hyperplasia
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.
Dysplasia
In addition to proliferating excessively these cells mutate which alters cell behaviour.
Metastasis
Cells mutate the ability to Lyse and gain access to circulatory system giving them access to the rest of the body.
Tumour cell characters
- 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
CANCER CLASSIFICATION - Grade
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
CANCER CLASSIFICATION- Stage
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
Genetic and Molecular basis of CANCER
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.
Cell division and its control
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.
Mutations and cancer
Control of cell division is regulated in 2 ways:
- Genes that suppress cell division -Tumour suppressor genes - control abnormal cell proliferation and therefore suppress tumorigenesis e.g. p53, RB1
- Genes that promote cell division (proto-) Oncogenes promotes cell proliferation and differentiation, e.g. growth factors, transmembrane kinase, signal transducers
Knudsons 2 hit hypothesis
Sporadic - takes time to inactivate both copies of the allele
Hereditary - one copy already inactivated so cancer develops much faster.
STAGES OF CANCER DEVELOPMENT
INITIATION-irriversible alteration in the cell’s genetic structure
PROMOTION-second cell mutation
PROGRESSION-increased growth rate, invasiveness, cell proliferation and metastasis
Environmental factors
Diet/lifestyle (eating, breathing, sex, sun, alcohol)
Tobacco
Viruses (HIV, HepB, HPV)
Occupational exposure
ROLE OF IMMUNE SYSTEM
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.
Breast Cancer
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
Colon Cancer
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
Colon cancer
- 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.
SEVEN WARNING SIGNS OF CANCER
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
Biochemical impacts of cancer on the body
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
CANCER- screening
- 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
CANCER TREATMENT
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?
CANCER – summing it up
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
