Cancer 2 Flashcards
Multiple genetic changes…
…cause cancer.
Knudson proposed that carcinogenesis requires…
…2 hits
What are the first events/hits of carcinogenesis?
- 1st event – initiation
— Carcinogen = initiator
Whats the second event/hit of carcinogenesis?
- 2nd event - promotion
— Agent - promoter
Each hit produces…
a change in the genome which is transmitted to its progeny (ie. clone)
Whats a lag period?
Time between exposure (first hit) and development of clinically apparent cancer
Altered cell shows no …
… abnormality during lag period
Multiple mutations lead to…
…colon cancer
Angiogenesis is the…
…growth of blood vessels from the
existing vasculature.
Angiogenesis is a …
… natural process involved in
healing and growth
Cancer cells need to develop a …
…blood supply in order to develop further
Until cancer develops a blood supply, they are mainly growing…
…anaerobically
Once a blood supply in a cancer has been established …
…they may undergo metastasis
What were the conclusions of the study titled “Is there a role for carbohydrate restriction in the treatment and prevention of cancer?”?
“Over the last years, evidence has accumulated suggesting that by systematically reducing the amount of dietary carbohydrates (CHOs) one could suppress, or at least delay, the emergence of cancer, and that proliferation of already existing tumor cells could be slowed down … In this review, we address the possible beneficial effects of low CHO diets
on cancer prevention and treatment.”
Define a Hit?
A hit is an event which causes a change in the DNA.
- point mutations / change in dna which causes rearrangements
What is metastasis?
the process by which cancer spreads from the place at which it first arose as a primary tumour to distant locations in the body.
Nine causes of death were described in cancer patients. These were:
- respiratory failure
- infection
- toxic drug reaction
- hepatic failure
- renal failure
- shock or heart failure
- adrenal gland failure
- electrolyte imbalance
- central nervous system
failure.
Describe the process of metastasis.
- Cancer cells invade surrounding tissues and blood vessels (perhaps from angiogenesis)
- Cancer cells are transported by the circulatory system to distant sites
- Cancer cells reinvade and grow at new location
Most cancers that arise from the accumulation of genetic changes
have a minimum of…
…6-9 different genes mutated
Cancer is not a…
…hereditary disease because we do not pass on cancer to offspring
We can inherit…
…dispositions (susceptibility) to cancer
BRCA 1 mutation (breast and ovarian cancer) is activated by…
…ATM kinases and targets
p53
- This is why it can run in families
What is BRCA 1 mutation involved in?
breast and ovarian cancer
The biggest issue is…
…mutation
anything that promotes mutation in a cell can increase your risk of …
…developing cancer
The main cause of mutation in cells are…
…oxidative stress
Factors that can increase oxidative stress include:
- Environmental toxins
- Infection
- UV radiation
- Radioactivity
- Immune disorders (inflammation)
- Stress
- Hypoxia
- Poor diet (deficient in antioxidants)
What are the conclusions of the study titled “Strategies for Reducing or Preventing the Generation of Oxidative Stress”?
“The most efficient preventive step to avoid exogenous free-radical exposure would be to avoid, as much as possible, exposure to endogenous and exogenous ROS generating compounds, including oxygen species, cigarette smoke, and UVR.”
“The reduction of oxidative stress could be achieved in three levels: by lowering exposure to environmental pollutants with oxidizing properties, by increasing levels of endogenous and exogenous antioxidants, or by lowering the generation of oxidative stress by stabilizing mitochondrial energy production and efficiency.”
“It also seems that by additional intake of synthetic antioxidants, total antioxidant activity in the blood/cells cannot be further increased or it cannot offer additional protection if one is having an optimal age, nutrition, and lifestyle.”
Define Hypoxia
when you havent got enough oxygen
A single mutation is often not…
…carcinogenic
- you also need other events to promote tumour formation
Events which cause promote tumour formation?
1) Initiation e.g. DNA damage
* Benzopyrene
2) Promotion e.g. Histologic change
* Turpentine (co-carcinogens)
3) Malignant transformation:
* Visible tumor formation – further DNA damage.
Symptoms of cancers?
1) Coughing, chest pain and breathlessness
2) Changes in bowel habits
* diarrhoea or constipation for no obvious reason
* a feeling of not having fully emptied your bowels after going to the toilet
* pain in your stomach or back passage (anus)
3) Bloating
4) Unexplained Lump e.g., in the breast (may also apply to men)
5) Unexplained weight loss
6) Bleeding
* From places that you do not expect to bleed or outside usually menstrual cycle
7) Moles
* changes shape or looks uneven, changes colour, gets darker or has more than 2 colours
* starts itching, crusting, flaking or bleeding
* gets larger or more raised from the skin
Treatments of cancer?
1) Surgery
- Remove cancerous tissue
2) Chemotherapy
- Targets dividing cells, may target specific tissues
- Side effects due to killing cells that normally divide (e.g., hair follicle)
3) Radiotherapy
- Targeted beam of radiation directed at the tumour to promote death.
- Will also affect surrounding tissues
4) Hormone therapy
- Inhibit normally produced hormones to remove the stimulus for the tumour growth (e.g., oestrogen antagonists)
5) Targeted cancer drugs
- Specific drugs to inhibit or kill cancer cells
6) Stem cell and bone marrow transplants
- For replacing functional cells containing a cancerous cells that have been killed by other treatments (e.g., leukaemia treated by chemotherapy)
7) Immunotherapy
- Direct the person’s immune system to seek out and destroy specific types of
cancer cell
In lifestyle adjustment, the major aim is…
…preventing &/or reducing inflammation
Antioxidants work…
…together
Conclusions of the study titled “Epigenetics: A new link between nutrition and cancer”?
“Emerging studies suggest that dietary components can affect gene expression through epigenetic mechanisms … The
potential reversibility of epigenetic changes suggests that they could be modulated by nutrition and bioactive food compounds. Thus, epigenetic modifications could mediate environmental signals and provide a link between susceptibility genes and
environmental factors in the etiology of cancer.”
Conclusions of the study titled “DNA methylation, an epigenetic mechanism connecting folate to healthy embryonic development and aging”?
“During aging, genomic and gene-specific DNA methylation can be altered in a tissue-specific manner. Folate status further modifies DNA methylation in the elderly. It appears that aging and folate deficiency synergistically provide an epigenetic milieu toward cancer development.”
Epigenetic changes due to Ageing?
- Genomic DNA hypomethylation
- Promoter DNA hypermethylation in tumour suppressor genes
- Histone modifications
Genetic changes due to ageing?
- Genetic mutations
- Mitochondrial DNA deletion
- Shortening telomere length
Conclusions of “The fraction of cancer attributable to lifestyle and environment factors in the UK in 2010”?
“The overall objective of the study is to estimate the percentage of cancers (excluding non-melanoma skin cancer) in the UK in 2010 that were the result of exposure to 14 major lifestyle, dietary and environmental risk factors… a section for each of the 14 exposures,
followed by a Summary chapter, which considers the relative contributions of each factor to the total number of cancers diagnosed in the UK in 2010 that were, in theory, avoidable”
“This chapter summarises the results of the preceding sections, which estimate the fraction of cancers occurring in the UK in 2010 that can be attributed to sub-optimal, past exposures of 14
lifestyle and environmental risk factors… For each of 18 cancer types, we present the percentage of cases attributable to one or all of the risk factors considered.”
“Exposure to less than optimum levels of the 14 factors was responsible for
42.7% of cancers in the UK in 2010 (45.3% in men, 40.1% in women) – a total of about 134000 cases.”
“In men, deficient intake of fruits and vegetables (6.1%), occupational exposures (4.9%) and alcohol consumption (4.6%) are next in importance, while in women, it is overweight and obesity (because of the effect on breast cancer) – responsible for 6.9% of cancers, followed by infectious agents (3.7%).”
