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Molecular basis of disease > Overview of Cancer: L1 > Flashcards

Overview of Cancer: L1 Flashcards

1
Q

What is cancer?

A

Cancer is a group of diseases that are characterised by uncontrolled and spread of abnormal cells. If the spread is not controlled, it can result in death.

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2
Q

What is dysplasia?

A

It is the change in shape or morphology or cytology which causes cells to grow into large masses of unusual sizes.

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3
Q

What are the steps leading to invasive cancer? Hint 5

A
  1. Cell with genetic mutation
  2. Hyperplasia
  3. Dysplasia
  4. In situ cancer
  5. Invasive cancer
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4
Q

What is the name of cancer that kills patient and normally what we think of when we refer to cancer?

A

Malignant cancer

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5
Q

What is a neoplasm?

A

A tumour

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6
Q

What can neoplasms be?

A

Neoplasms can be benign, premalignant or malignant

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7
Q

What is the cause of cancer?

A

The main causes of cancer remain largely unknown however there are many factors known to increase risk

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8
Q

What are these risk factors?

A

Some of these risk factors are modifiable such as tobacco use and excess body weight, while others are generally unmodifiable such as inherited mutations and immune conditions

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9
Q

Is cancer a complicated process?

A

Yes, cancer is a complex disease and it is a sequential series of events leading to it, it is not caused by just one event

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10
Q

What is statistic for cancer?

A

1 in 2 get cancer at some point in their life

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11
Q

What is the leading cause of death in developed countries?

A

Cancer is the leading cause of death in developed countries and the 2nd leading cause of death worldwide

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12
Q

Stats for Cancer in 2018:

A

17 million cancer cases and 9.5 million cancer deaths estimated worldwide by IARC - International agency for research on cancer

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13
Q

What are the 3 costs of cancer?

A

Human toll
Financial costs
Costs will increase with growing ageing populations

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14
Q

What is a societal concern for cancer?

A

Major societal concern in forthcoming years as ageing populations grow as 1 trillion US dollars per year and this will increase via new targeted therapies, etc.

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15
Q

What financial costs are associated with cancer? Hint 3

A
  1. There are direct costs such as treatment, care and rehabilitation
  2. Indirect costs such as loss of economic outcomes within morbidity and mortality costs
  3. Hidden costs such as health insurance and non-medical costs
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16
Q

Why is cancer increasing?

A

Main reason is that we are living longer, however lifestyle factors plays a role within this

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17
Q

What are the 4 ways that cancer is classified?

A

Cancer is classified by the origin of it such as breast, prostate, lung, etc
Then it is classified by tissue types
Classification by grade takes place
There is classification of cancer by its stage

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18
Q

How is cancer classified by tissue types?

A

By being either carcinoma (epithelia) and then falling under: adenocarcinoma (glandular epithelia) or squamous cell carcinoma (squamous epithelia).

Or by being sarcoma such as mesenchymal cells: muscle, bone, cartilage, fat, etc
Then split into Rhabdomyosarcoma, osteosarcoma, chondrosarcoma and liposarcoma

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19
Q

What has its own classification?

A

Blood cancers have their own classification

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20
Q

What are haematological disorders?

A

They are blood disorders

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21
Q

What 3 fall under haematological malignancies?

A

Leukaemia, Lymphoma and Myeloma

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22
Q

What is Leukaemia?

A

It is blood cancer which affects bone marrow

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23
Q

What is leukaemia split into?

A

Acute lymphocytic leukaemia, acute myeloid leukaemia, chronic lymphocytic leukaemia, and chronic myeloid leukaemia

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24
Q

What is Lymphoma?

A

Blood cancer that affects the lymphoid organs

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25
Q

What can Lymphomas be split into?

A

Hodgkin’s lymphoma and non-Hodgkin’s lymphomas such as indolent or high grade

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26
Q

What is myeloma?

A

It is blood cancer that affects plasma cells in the bone marrow

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27
Q

What does acute and chronic refer to?

A

Acute and chronic refers to how quick the onset of disease sets into patients

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28
Q

What does lymphocytic or myeloid refer to?

A

They refer to the lineage of cancer

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29
Q

What are high grade tumours?

A

They are more progressive versions of the disease and they are undifferentiated and highly abnormal

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30
Q

How are many cancer tumours classified?

A

Many cancers tumours are classified by their stage

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31
Q

What does it mean when cancer is classified by Grade?

A

Grade describes tumours by their cell dfferentiation

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32
Q

What are tumours split into?

A

Into low grade tumours or high grade tumours

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33
Q

What are low grade tumours?

A

They are well differentiated and they closely resemble normal specialized cells.

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34
Q

What are the 4 Grades of cancer?

A
  1. Well differentiated cells with slight abnormality
  2. Cells are moderately differentiated and slightly more abnormal
  3. Cells are poorly differentiated and very abnormal
  4. Cells are immature and primitive and undifferentiated
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35
Q

What does it mean to classify cancer by stage?

A

This describes cancer by the extent or severity of it

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36
Q

What does classification by stage involve?

A

It involves TNM staging where T stands for tumour size, N stands for the degree of regional spread or node involvement and M stands for distant metastasis

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37
Q

What are the different TNMs and what do they mean?

A

T0 - no evidence of tumours
T1-4: increasing tumour size and involvement
N0 - No nodal involvement
N1-4: Increasing degrees of lymph node involvement
M0- no evidence of distant tumours
M1-4: evidence of distant spread of tumour

38
Q

What does ALL stand for and discuss it?

A

ALL stands for acute lymphoblastic leukaemia
Treatments are very effective and 90% of patients will be cured from the disease

39
Q

What does FL stand for and discuss it?

A

FL stands for Follicular Lymphoma
Patients might die with disease rather than from the disease, however it may transform into a more aggressive form of the disease. They will look like pretty normal cells except the lymph nodes which will be packed full

40
Q

How are cancers distinguished from one another ? hint 5

A

By parameter, clinical, morphology, immunophenotype, and molecular/genetic

41
Q

Explain how ALL is split up into these 5:

A

Parameter is acute lymphoblastic leukemia
Clinical shows it is mostly found in children in the bone marrow and blood and that it is aggressive but curable
Morphology shows lymphoid blasts
Immunophenotype is B-lineage progenitors
Molecular/Genetic analysis usually shows no lgH rearrangement and translocations seen mainly at chromosomes at 12/21

42
Q

Explain how FL is split into these 5:

A

Parameter is Follicular Lymphoma
Clinical analysis shows FL mainly in older patients, observed at lymph nodes. It is indolent but incurable and it may transform into more aggressive disease
Morphology shows follicle centre cells
Immunophenotype shows mature B cells
Molecular/genetic analysis shows cloncal lgH rearrangement with somatic lg mutations and translocations observed at chromosomes 14 and 18

43
Q

What are the causes of cancer?

A

Cancer is a genetic disease caused by mutations, chromosomal abnormalities and epigenetic effects which effect genes that cause control growth, cell division and cell death
Cancer is caused by external and internal factors

44
Q

Are cancers preventable?

A

Over 50% of cancers are potentially preventable

45
Q

What are external factors causing cancer?

A

Tobacco, chemicals, radiation, infectious organisms, etc

46
Q

What are internal factors causing cancer?

A

Inherited mutations, hormones, immune conditions, etc.

47
Q

What is the number 1 risk factor?

A

Age - 78% of all newly diagnosed cancer cases in developed countries happens at ages 55 or greater

48
Q

What are the risk factors? Hint 11

A
  1. Age
  2. Exposure to carcinogens
  3. Alcohol
  4. Chronic inflammation
  5. Diet
  6. Immunosuppression
  7. Infectious agents
  8. Obesity
  9. Radiation
  10. Sunlight
  11. Tobacco
49
Q

What are the risk factors for breast cancer? Hint 8

A
  1. Age
  2. Presence of a substantial family of breast cancer
  3. Mutations in breast cancer susceptibility genes: BRCA1+BRCA2 account for 5-10% of all breast cancer
  4. Long menstrual history
  5. Never having children
  6. Recent use of oral contraceptives
  7. Having one’s first child after age 30
  8. Obesity after menopause
50
Q

What percent of breast cancer is caused by BRCA mutations?

A

5-10% of breast cancer is caused by these mutations

51
Q

Are there other cancer susceptible genes, or is it only from BRCA mutations?

A

There are other cancer susceptible genes it is not all these BRCA mutations

52
Q

What are BRCA genes?

A

They are unrelated tumour suppressor genes. They are involved in DNA repair of double stranded breaks, so they are genes which function allows them to stop cellular change to cancer, so they are involved in DNA repair.

53
Q

What is the issue with BRCA mutations in relation to cancer?

A

Cancer is a genetic disease and anything that affects the repair of double stranded breaks will increase changes of developing cancer.

54
Q

What do inherited mutations in BRCA1+2 predispose someone to?

A

Inherited mutations in BRCA1+2 predispose to high risks of breast and ovarian cancer

55
Q

What are lifetime risks of breast cancer with BRCA mutations?

A

They can be as high as 80%.

56
Q

What are lifetime risks of ovarian cancer with BRCA mutations?

A

Lifetime risks of ovarian cancer are greater than 40% for carriers of the BRCA1 mutation and greater than 20% for carriers of the BRCA2 mutation

57
Q

What percent of ovarian cancer are due to inherited mutations in BRCA1+2?

A

10-15% of ovarian cancer cases are due to inherited mutations in BRCA1+2

58
Q

What is another inherited mutation that influences risk of breast cancer?

A

ATM, BARD1, etc.

59
Q

What are the risk factors for prostate cancer?

A

Age, race, family history

60
Q

What are the risk factors of colorectal cancer?

A

Age, history of chronic inflammatory bowel disease, obesity, diet high in red and processed meat, smoking, heavy alcohol consumption

61
Q

What are the risk factors of stomach cancer?

A

50% of new cases due to H. pylori infection, smoking

62
Q

What are the risk factors of lung cancer?

A

80% of cases in men and 50% in woman worldwide due to smoking

63
Q

What are the risk factors of liver cancer?

A

Strongly associated with chronic hepatitis B and C infection (>50%)

64
Q

Who has a higher rate of prostate cancer in the US, White/African American/Asian men?

A

African America in US have higher rate of prostate cancer when compared to white and Asian men

65
Q

What can decrease the incidence of colorectal cancer?

A

Decreasing alcohol and wine consumption can decrease the incidence of colorectal cancer

66
Q

What is the number one risk factor for lung cancer?

A

Smoking

67
Q

What percent of lung cancer is due to smoking in men and women?

A

80% in men and 50% in women of lung cancer worldwide is due to smoking and the incidence of women is increasing each year

68
Q

What type of process is cellular transformation?

A

Cellular transformation is a multistage process

69
Q

How do we get cancer? Using Blood Cancer is an example

A

Acute myeloid leukaemia:
- Normal blood cells which are stem cells in bone marrow or progenitor cells down by stem cells in differentiating cascade leading to myeloid cells.
Cells undergo a genetic event and in lots of cases this can be a gross genetic event such as a chromosomal translocation when you get a major defect in chromosomes
- 1st genetic deficit but can also be other ones and this causes other cells to accumulate inside here, and this altered genotype and can give rise to pre-leukaemic state of cells
- This first hit gives pre cancer cell some sort of survival advantage so it can grow and accumulate
- Second hit then happens, and this may be genetic mutations, aberrant microenvironment signals or epigenetic mutations such as methylation in gene promoters.
- Can give rise then to acute myeloid leukaemia a

70
Q

What is found in most cancer cells, is it all the same type of cell?

A

You find a ponderance of many cells, not just one type of cancer cell is found

71
Q

Can the microenvironment influence the development of cancer?

A

Yes the microenvironment can influence development of cancer

72
Q

How many mutations take place every day in the body?

A

70,000 per cell per day, mutations and DNA damage are common

73
Q

What are most of mutations?

A

Most mutations are repaired

74
Q

What do deleterious mutations lead to?

A

Deleterious mutations usually lead to cell death

75
Q

What can happen to some mutations?

A

Some mutations persist and can lead to cancer and these can be called driver mutations such as oncogenes and tumour suppressor genes.

76
Q

What is the other type of mutation called?

A

The other type of mutations are passenger mutations

77
Q

What are passenger mutations?

A

They are mutations which have no direct effect on cellular transformation, they can be silent or have a non-essential role in supporting transformation.

78
Q

What can proto-oncogenes do?

A

Proto-oncogenes perform physiological functions that are necessary for normal cellular homeostasis, such as processes of growth, proliferation, and survival

79
Q

What happens to proto-oncogenes during malignant transformation?

A

During malignant transformation regulation of the activity of proto-oncogenes is circumvented either by mutation or over-expression

80
Q

How many proto-oncogenes when mutated/over-expressed become oncogenes?

A

More than 200 proto-oncogenes when mutated or over-expressed become oncogenes

81
Q

What are some functions of proto-oncogenes?

A

Functions of proto-oncogenes include growth factors (PDGF, EGF), GF receptors (EGFR, HER2), signal transduction (RAS, ABL, RAF), transcription factors (MYC, FOS)

82
Q

What is the basic function of oncogenes?

A

Oncogenes promote growth

83
Q

What is another name for tumour suppressor genes?

A

Tumour suppressor genes are the opposite to oncogenes, they are anti-oncogenes

84
Q

What is the basic function of anti-oncogenes (TSGs)?

A

They suppress growth

85
Q

With TSG what is associated with malignancy?

A

Loss of inactivation associates with malignancy

86
Q

What to TSG and oncogenes work in concert to drive?

A

TSG and oncogenes work in concert to drive cellular transformation. Mutation and loss work together in cellular transformation into cancer

87
Q

Give some examples of TSGs:

A

TSG include BRCA1-2, APC, PTEN, TP53, Retinoblastoma

88
Q

How do TSG protect cells from transformation?

A

TSG protect cells from transformation by, for example controlling abnormal cell proliferation

89
Q

With cellular change from normal cell to a cancerous ones with colorectal cancer an example, what is an early event?

A

The mutation and loss of tumour suppressor gene: APC is an early event and this causes dysplasia in early adenoma.

90
Q

What is the second step towards colorectal cancer as the disease progresses?

A

Mutations occur in oncogenes such as KRAS and altered DNA methylation and this gives an intermediate adenoma

91
Q

After mutations in KRAS and altered DNA methylation, what is there a loss in for the 3rd step of colorectal cancer progression?

A

There is a loss in signal transduction of tumour suppressor genes such as SMAD2/4 associated of progression to late adenoma

92
Q

What is the final step and mutation of in the progression of colorectal cancer?

A

Finally, mutation and loss of TP53 tumour suppressor gene is associated with sequence of adenoma to carcinoma

Molecular basis of disease (2 decks)

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