Cancer Flashcards
(169 cards)
1
Q
what is cancer?
A
A complex group of >100 diseases affecting a wide range of tissues
Caused by mutations in genes controlling cell growth after exposure to carcinogens
2
Q
Most cancer mutations are in somatic cells but many cancers cluster…
A
…..in families
- Shared environment and genes
- 1% of mutations are inherited – but extra somatic mutations also required
3
Q
Cancer is characterised by
A
- Loss of growth control leading to an unregulated increase in cell number
- Metastasis and invasion of other tissues
4
Q
Cancers differ in:
A
- Tissue of origin
- Causal factor(s)
- Molecular mechanisms
5
Q
Incidence & importance
A
-Cancer affects 1 in 3 people worldwide -Leading cause of death in NZ and second worldwide -According to the Ministry of Health in NZ in 2015: Incidence (number of cases/year): 23,215 Mortality (number of deaths/year): 9,615 -About 1/2 the number of people that get cancer will die from it
6
Q
Development of cancer
A
– benign vs malignant
7
Q
- neoplasia
A
Tumour that starts when cells that have
lost growth control proliferate to form a
new growth
8
Q
Cells do not die via
A
apoptosis, which
normally keeps the number of cells
constant
9
Q
Tumour is benign if
A
the neoplastic cells
are clustered in a single mass
10
Q
Tumour becomes malignant once
A
cells
have undergone metastasis
11
Q
Benign tumours
A
-Cells that are well differentiated and look like normal cells
-May perform the normal function of the tissue. e.g. secrete hormones, although may over-secrete - insulinoma
-Cells grow relatively slowly but this is not supressed by apoptosis or
contact inhibition
-Size may be limited to just a few mm by lack of blood supply
-Surrounded by a fibrous capsule & confined to original location
-Do not infiltrate, invade, or metastasize
-Can damage nearby organs by compressing them
12
Q
Malignant tumours
A
-Cells are less differentiated and do not look like normal cells
-Do not perform the normal function of the tissue
-May secrete new signalling molecules, enzymes or toxins etc.
-Cells grow rapidly since they have lost the ability to control
proliferation and differentiation
-No fibrous capsule
-Cells infiltrate & invade surrounding tissues and metastasize to
form new tumours at distant sites
-Tumour sends “legs” into surrounding tissue
-Gives name to Cancer = Crab, -based on these legs
-Can compress and/or destroy surrounding tissues
13
Q
Tumour growth can be
A
very rapid
14
Q
Tumour classification
A
according to tissue of origin
15
Q
Benign tumours
A
Tissue name + “-oma”
16
Q
Malignant tumours (cancers)
A
Carcinomas
Adenocarcinomas
Sarcomas
Leukaemias
17
Q
Carcinomas
A
are derived from epithelial cells. – the most common type of cancers
18
Q
Adenocarcinomas
A
are derived from glandular epithelial cells
19
Q
Sarcomas
A
are derived from mesenchymal cells
20
Q
Leukaemias
A
are derived from haemopoietic cells
21
Q
Carcinomas: Examples
A
Adenocarcinoma, Squamous cell , and others
22
Q
Carcinomas:Adenocarcinoma
A
Lung, colon, breast,
pancreas, stomach,
oesophagus, prostate,
ovary
23
Q
Carcinomas:Squamous cell
A
Skin, oropharynx, larynx,
lung, oesophagus, cervix
24
Q
Carcinomas:Others
A
Small-cell lung-, large cell lung-, haptic-, renal and bladder- carcinomas
25
Control of cell number: Most cells in adult tissues are
terminally differentiated and
| quiescent (non-dividing). exceptions include; hair follicles, blood and gut stem cells
26
Control of cell number: Within each tissue, cell death, by apoptosis or necrosis, is
balanced by
cell division, often of stem cells, leaving the total
| number of cells constant
27
Control of cell number: Cell division is tightly regulated by
growth factors which allow
| quiescent cells to enter the cell cycle and divide
28
Control of cell number: If differentiated cells start dividing again or dividing cells lose control of
growth then this can lead to cancer
29
Properties of Normal Cells
-Dependent on growth factors for cell division
-Cells have a finite number of cell divisions
-Contact inhibition of growth
-Cells need to be stuck down to the
Extracellular Matrix (ECM) to survive
-DNA damage, cell stresses and detachment for the ECM can cause death by apoptosis
-Cells usually stay in one place
-Have a stable genome
-Depend on normal blood supply
30
Properties of Tumour cells
-Able to divide in the absence of growth factors
-Cells have unlimited number of cell divisions
-No contact inhibition of growth
-Cells have impaired cohesiveness/adhesion
and show anchorage independent growth
-Tumour cells evade apoptosis
-Cells can invade other tissues and migrate to other parts of the body (metastasis)
Have an unstable genome due to defects in
sensing DNA damage and repairing it
-Secrete factors to stimulate new blood vessel growth as the tumour grows
31
Telomere length helps control
cell lifespan
32
Cells contain telomerase, an enzyme which
can elongate telomeres
33
Telomerase activity is essential for
allowing cells to keep proliferating
34
As cells age, telomerase becomes
inactive and hence telomeres shorten & cells lose the ability to divide – limits lifespan
35
Increased telomerase activity allows cells to
proliferate indefinitely and leads to cancer
36
Cell proliferation is regulated by transit through
| the
cell cycle
37
Four phases OF Cell proliferation:
- G1 – gap between M & S phase
- S phase – DNA synthesis/replication
- G2 – gap between S & M phase
- M phase – mitosis, cytokinesis/division
38
Cell proliferation: In adult most cells are terminally differentiated
and
no longer divide - quiescent (G0)
39
If differentiated cells start dividing again or
| cycling cells lose control then this can lead to
uncontrolled proliferation & cancer
40
Transit through cycle regulated by
checkpoints
41
Cell cycle checkpoints control
cell growth
42
Progression through cell cycle checkpoints controlled by
Cyclin Dependent
| Kinases (CDKs) and CDK inhibitors
43
Cyclin Dependent
| Kinases (CDKs) and CDK inhibitors ensure:
- Correct sequence of phases (G1, S, G2, M)
- Cellular and environmental conditions are favourable
- DNA is properly replicated and undamaged
44
G1/S transition checkpoint
Are growth factors present?
Are nutrients available?
Is DNA damaged?
Is the cell big enough?
45
G2/M transition checkpoint
Has DNA replicated?
| Is DNA damaged?
46
Checkpoint failure causes
cell-cycle arrest and can lead to cell death by apoptosis
47
G1/S Checkpoint is regulated by
Growth Factors and DNA damage
48
Transit through the G1/S
| checkpoint requires an
an active Cdk4/6-cyclinD complex
49
Cdk4/6 is activated by
growth factors
50
p21 & p27 are
Cdk inhibitors that
| inhibit Cdk4/6
51
p53 is a transcription factor
| induced by
DNA damage that
| controls expression of p21 and p27
52
p53, p21 & p27 are examples of
Tumour Suppressors as they inhibit
| cell division
53
Cells need growth factors and
intact DNAto progress through G1/S
54
Cancer is caused by mutations in genes controlling
cell number
- Mutations that enhance cell proliferation
- Mutations that supress cell death (apoptosis)
55
Mutation of DNA repair genes causes
genome instability
| -makes further mutations more likely
56
Most mutations are somatic and acquired by
environmental interactions
| -e.g. exposure to carcinogens and lifestyle factors
57
Some germline mutations may be inherited and predispose someone to
cancer e.g.
Rb – retinoblastoma, BRCA1/2 – breast cancer
58
A single mutation is not enough. Each cancer arises from an
accumulation of several mutations over a lifetime – “multi-hit hypothesis”
- From 2 to 20 depending on the type of cancer
- Colon (4-5), Lung (10-15)
59
Identifying inherited mutations allows
screening for individuals
| who are at particular risk (e.g. BRCA1/2 for breast cancer)
60
Sequencing genes mutated in cancers can give a
molecular
fingerprint for each cancer (a list of genes which are mutated)
-Diagnosis and targeted treatments
-Understanding mechanism and development of new therapies
61
Many genes mutated in cancer identified since the
early 1970s
62
Fall into two main types, which positively & negatively regulate cell proliferation
- Oncogenes
| - Tumour suppressor genes
63
First genes identified were termed
oncogenes – genes that cause cancer
64
Oncogenes are mutated forms of the normal genes that
positively regulate cell division - proto-oncogenes
65
Proto-oncogenes encode components of
growth factor signalling pathways that stimulate cell proliferation by allowing progression from G0/G1 into S-phase when growth factors are present
66
Examples of proto-oncogenes
```
Growth factors (EGF) & receptors (HER2)
Signalling proteins (Ras) & protein kinases (Src, Abl)
Transcription factors (Myc, Jun, Fos)
```
67
Mutations can be point mutations, insertions, deletions, translocations
etc, but cause a
gain of function in which the protein is increased in expression or activated in the absence of growth factors
68
This stimulates cell proliferation in the
absence of growth factors
| e.g. Ras-MAPK pathway > > > G1/S transition
69
Tumour suppressor genes
were identified later (1980/90s)
70
Tumour suppressor genes negatively regulate
Tumour suppressor genes negatively regulate
71
Usually encode proteins at
cell cycle checkpoints that block progressionthrough G1/S and G2/M if there is a problem
- p53, p21/27 – prevent cell division if DNA is damaged (G1/S & G2/M)
- p21/27, Rb, E2F – prevent G1/S transition if no growth factors
72
Mutations cause a
loss of function (decreased expression or no activity)
73
Mutations Usually requires
both alleles to be inactivated since some normal protein may allow the checkpoint to function
-Knudson’s two-hit hypothesis for retinoblastoma (Rb inactivation)
-This allows cells to progress through the cell cycle in the absence of
growth factors, with DNA that is damaged or not fully replicated
74
Given that the Ras-ERK and PI3K-Akt signaling pathways are activated by growth factors such as
EGF, IGF, and fibroblast growth factor (FGF), which play major roles in control of cell fate, they can thus be considered developmental signaling pathways that are hijacked in cancer.
75
Growth factors activate the
Ras-MAPK pathway
-This activates Cdk4/6 and allows
progression through the G1/S
checkpoint and cell division
76
In 30% of all cancers, activating
| mutations are found in the
Ras protein
77
In cells with activated Ras the pathway
| is always
active and cell division is independent of growth factors
78
The normal Ras gene is therefore a
proto-oncogene and the activated form
| an oncogene
79
p53 is a sensor for
DNA damage
80
p53
“the guardian of the genome"
81
Transcription factor activated by
DNA damage
-Causes cell-cycle arrest if DNA is damaged by
upregulating expression of p21 and p27 that inhibit Cdk4/6 and the G1/S transition
82
p53 Allows time to repair
DNA damage
| -If damage is extensive cell dies by apoptosis
83
50% of all human cancers have inactivating mutations in p53, mainly in
DNA binding domain
84
p53 Allows cell division when
DNA is damaged
85
p53 is a
tumour suppressor gene (TSG)
86
Types of mutations
-Some may be inherited e.g.
mutations in Rb give rise to
retinoblastoma
-Most are sporadic, due to
environmental factors
-Multiple mutations are required
for full cancer phenotype
-Mutation of genes involved in
DNA repair is common and gives
rise to genome instability which
make further mutations likely
87
Stages of cancer development
- Initiation
- Promotion
- Progression
88
Stages of cancer development-Initiation
Exposure to a chemical or physical carcinogen
-Activation or inactivation by metabolism
or excretion
Damage to DNA
-May be repaired or cause cell death
Proto-oncogene activation or tumour
suppressor inactivation
89
Stages of cancer development-Promotion
Altered cells stimulated to divide by a tumour promoter
-Altered cell may remain dormant or be
removed by immune system
90
Stages of cancer development-Progression
-Develop more mutations
-Uncontrolled cell replication and loss of
specialisation
-Cells are more aggressive and invasive
91
intravasation
```
Cells in a primary tumour develop the
ability to escape into the circulation -
-Loss of adhesion
-Secretion of proteases to degrade
basement membrane
-They survive and travel in the blood or
lymphatic system
```
92
Extravasation
Exit into surrounding tissues via proteases –
-Develop into a secondary tumour or
metastasis
93
Growth of new blood vessels
| (angiogenesis) enables the tumour to
grow rapidly
Metastasis to multiple distant sites and
rapid growth are life threatening
94
Host risk factors
- Hereditary predisposition
- Reproductive hormones – can act as tumour promoters
- Obesity
- Immune surveillance of tumour antigens
95
Environmental risk factors
- Chemical carcinogens (mutagens)
- Viruses & bacteria
- Radiation
96
A diet rich in fruit and vegetables
seems to protect against many
cancers due to
plant secondary
metabolites responsible for the
flavour and colour of plants called
phytochemicals
May protect by blocking effects of
carcinogens or suppressing
growth of tumour cells
97
food Blockers
Flavanols – Green Tea
| Glucosinolates - cruciferous plants: cabbage family, radishes, mustard, water cress
98
food Suppressors
Genistein (soy), gingerol (ginger), limonene (citrus), resveratrol (red wine),
glycyrrhizin (liquorice ), curcumin (cumin), aspirin (willow bark)
99
Clinical manifestations – local effects
Mainly physical effects due to compression or blockage of structures close by:
Neurological problems due to compression of structures by brain tumours
Intestinal obstruction due to a colon carcinoma
100
Clinical manifestations – local effects: Blood vessels
Blockage or bleeding
101
Clinical manifestations – local effects: Effusions – build up of fluid
-Pleural effusion due to metastatic cancer cells growing in between lung
plural membranes, -also pericardial effusion
-Ascites – build up of fluid in peritoneal cavity – peritoneal carcinoma
102
Clinical manifestations – systemic effects: Various types of malnutrition
Malabsorption
Anaemia
Anorexia & Cachexia
103
Clinical manifestations – systemic effects:
Fluid and electrolyte imbalances
| Fatigue and sleep disturbances
104
Clinical manifestations – systemic effects: Paraneoplastic syndromes
Symptoms unrelated to the initial tumour site
| Ectopic hormones or factors secreted by tumour cells
105
Clinical manifestations – systemic effects: Pain
mainly in the later stages
106
Cancer anorexia-cachexia syndrome
-Protein/energy malnutrition due to:
-Increased energy demand of rapidly
growing cancer cells (glucose)
-Reduced energy intake & malnutrition
Loss of appetite
Altered taste
Reduced absorption
-Not completely explained by energy demands of tumour
-Pro-inflammatory cytokines (TNFα, IL-1, IL-6) also supress appetite
107
Cancer anorexia-cachexia syndrome: Death may occur due to
cachexia linked starvation rather than the actual cancer
Early active nutritional intervention is important
- Increased energy & protein
- Small, frequent, easily digestible meals, not bulky low energy high fibre foods!
Unexplained weight loss may mean an undiagnosed cancer
108
Paraneoplastic syndromes
rare disorders that are triggered by an altered immune system response to a neoplasm. They are defined as clinical syndromes involving nonmetastatic systemic effects that accompany malignant disease.
see lecture notes
109
Seven warning signs of cancer
C.A.U.T.I.O.N.
110
C.A.U.T.I.O.N.
C-hange in bowel or bladder habits
A- sore that does not heal
U-nusual bleeding or discharge from any body orifice
T-hickening or a lump in the breast or elsewhere
I-ndigestion or difficulty swallowing
O-bvious change in a wart or mole
N-agging cough or hoarseness
111
Screening & diagnosis
```
Indirect, non-specific tests
Cytology
Diagnostic imaging
Tumor markers
Microarray technology
```
112
Screening & diagnosis:Indirect, non-specific tests
Liver function, abnormal hormones, blood count, blood in stools, sudden
unexplained weight loss, etc
113
Screening & diagnosis: Cytology
Pap smear, tissue biopsy, bone marrow
Immunohistochemistry – e.g. estrogen or EGF receptor
114
Screening & diagnosis: Diagnostic imaging
X-rays e.g. chest or mammogram, computed tomography - CT scan
Magnetic Resonance Imaging - MRI
Ultrasound
115
Screening & diagnosis: Tumor markers
e.g. prostate-specific antigen (PSA)
Need confirmation & to be done regularly to monitor progression of disease
116
Screening & diagnosis: Microarray technology
Gene chips to measure mRNAs
Check expression of specific cancer-associated genes (oncogenes & TSGs)
117
Specific tumour markers
molecules produced by tumor cells or other cells of the body in response to cancer or certain benign conditions. Most tumor markers are secreted into blood and may be estimated in blood, but they may also be measured in urine, tissues etc.
see lecture notes
118
Tumour grading
Microscopic/histologic examination of cells appearance and state of
differentiation and number of mitotic cells (Grade I – 4)
119
Tumour grading:
Grade l - Cells differ slightly from normal cells and are 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
120
Tumour staging
Clinical, radiographic, surgical examination of extent and spread of
tumour to help with treatment and prognosis
Specific for each type of cancer
121
Tumour staging: TNM staging
T 1 – 4 = tumour size
N 0 – 3 = lymph node involvement
M 0 – 1 = metastasis
122
Tumour staging: Overall Stage Grouping - American Joint Committee on Cancer (AJCC)
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 to distant sites
123
Prevention
Avoidance of environmental exposure
Diet, smoking, alcohol, obesity etc
Products e.g. sunscreen, sunhats, clothing
Vaccination - HPV
Routine screening - smear, mammography, fecal occult
blood test, gene screen, protein profile etc
Education & Health promotion programmes
Ministry of Health
Cancer Society
NZ Cancer Strategy
124
Treatment I: Surgery
Determined by extent of disease
Excellent if no metastasis and detected early enough
May trigger metastasis?
125
Treatment I: Radiation therapy
Repeated low doses from a beam, implantation of a radioactive
source (brachytherapy) or systemic administration of radioisotopes
Generates DNA strand breaks through free radical formation
Cell dies by the apoptopic pathway
Not so effective if the tumour has mutations in the p53 tumour
suppressor gene
126
Treatment II: Chemotherapy
Major treatment that targets rapidly dividing cells
Multiple rounds
Combinations of drugs help with resistance
Often combined with radiation therapy
Side effects – anaemia, hair loss, nausea/vomiting
127
Treatment II: Hormone and anti-hormone therapy
Cancers responsive to / dependent on hormones
128
Treatment II:Immunotherapy
Stimulate the immune system to kill cancer cells
Cytokines, cancer vaccines etc
Administer sensitized NK cells or T-cells (CAR-T cells)
129
Treatment II: Immunotherapy
Stimulate the immune system to kill cancer cells
Cytokines, cancer vaccines etc
Administer sensitized NK cells or T-cells (CAR-T cells)
130
Treatment II: Targeted therapies
Mainly monoclonal antibodies that target specific proteins/processes
Bevacizumab binds VEGF receptor - blocking angiogenesis
Trastuzumab (Herceptin) binds HER2 - overexpressed in 20-30% breast cancers
131
Cancers in New Zealand
```
NZ has a growing & ageing population
More people are developing cancer
In New Zealand, about 1 in 3 people who get cancer are cured
Most prevalent cancers in NZ
1. Lung – biggest cause of cancer in NZ
2. Bowel – NZ has one of highest rates in world
3030 people were diagnosed and 1191 died in 2011
3. Breast
Around 600 deaths per year
Skin
Prostate
Cervical
```
132
Lung Cancer: Incidence
Occurs most often in adults 40 - 70 yrs old
Most common cause of death for men and second most common for women in NZ
Usually diagnosed late & after metastasis, but people can survive if caught early
133
Lung Cancer: Risk factors
80-90% due to long term exposure to carcinogens in tobacco smoke (Polycyclic
Aromatic Hydrocarbons – PAHs)
Passive smoking may also cause lung cancer but still not clear
Occupational exposure
Asbestos; processing of steel nickel chrome and coal gas; radiation; radon gas
134
Lung Cancer: Signs & symptoms
Persistent, worsening cough
Coughing up excessive phlegm with blood
Chest pain with coughing or breathing
Recurring chest infections
135
Lung Cancer: Diagnosis
Symptoms; health and work history - smoking and other
exposure; physical exam; then decide on tests
Chest x-ray, CT scan
Sputum cytology
Bronchoscopy
Fine needle aspiration of tumour
Thoracentesis – check pleural fluid for cancer cells
Mediastinoscopy – biopsy of lymph nodes in mediastinum
136
Lung Cancer:Prevention & treatment
Cessation of smoking
Surgery
Radiation
Chemotherapy
137
Bowel Cancer:Incidence
New Zealand has very high rate (3030 cases in 2011)
Occurs most often in adults 50+ yrs old, slightly more prevalent in men
Early detection and treatment gives 90% chance of long term survival
138
Bowel Cancer:Risk factors
Increasing age & low fibre, high fat diet
Inflammatory bowel > 10yrs (e.g. ulcerative colitis)
Familial Adenomatous Polyposis (FAP) ~ 1% of cases
-Mutations in the Adenomatous
-Polyposis Coli (APC) gene
Rapid tumour initiation, slow progression
Hereditary nonpolyposis colorectal cancer (HNPCC) ~ 2-4% of cases
-Slow initiation, rapid progression
139
Bowel Cancer:Signs & symptoms
Blood in bowel motions or change in bowel habits for several weeks
Abdominal discomfort e.g. bloating, cramps etc
Unexplained weight loss, tiredness, anaemia
140
Bowel Cancer:Diagnosis
Rectal and abdominal exam
Blood tests
Colonoscopy; CT colonography etc
141
Bowel Cancer:Prevention
Maintain a healthy diet & weight
Regular exercise
Quit smoking & cut back on alcohol
Bowel screening helps earlier detection
-Fecal blood test
-NZ pilot in 2011, rolled out in 2017
-Available for all 60-74 yr olds by 2020
142
Bowel Cancer:Treatment
Surgery
Radiation
Chemotherapy
143
Breast cancer:Incidence
Most common cancer in women (1 in 9 will be affected)
Most will have no family history
~ 3000 new diagnoses each year (20 in men) with ~ 600 deaths
144
Breast cancer:Signs & symptoms
```
Change in breast shape or lumps in breast
Thickening of tissue
Nipple changes e.g. skin dimpling
Blood stained discharge from nipple
Rash
Painful area
```
145
Breast cancer – risk factors: Host risk factors
Being female
Age – 70% of cases will be 50+ yrs
Having previously had breast cancer
Increased number of abnormal cells in milk ducts
Affected first degree relative (risk doubles)
Mutation of BRCA1 (Chr 17) and BRCA2 (Chr 13) genes
Both are TSGs involved in DNA repair
-10% of all breast cancers – the rest are sporadic
-Found in 33% of women with breast cancer under 29, only 2% in 70+ yrs
-BRCA1 – predisposes to breast and ovarian cancer
-BRCA2 – predisposes to breast cancer only
146
Breast cancer – risk factors:Environmental risk factors
Nulliparity – not having given birth
First child after 30
High fat diet, alcohol use
Oestrogen replacement therapy
147
Breast cancer – hormone and growth factor receptors: Circulating oestrogen and progesterone
Can act a tumour promoters if receptor is present
Oestrogen receptors (ER) expressed in ~80% of
breast cancers
Progesterone receptors (PR) expressed in ~60%
of breast cancers
148
Breast cancer – hormone and growth factor receptors:Amplification of HER2
Human Epidermal growth factor Receptor
(HER2/neu) overexpressed in ~15-30% of breast
cancers
Associated with shorter disease-free survival and
overall survival
Acts as an oncogene
-Activates growth factor signalling pathways
associated with cellular proliferation,
survival, angiogenesis and invasion
149
Breast cancer:Diagnosis
Medical history; physical exam; mammogram/ultrasound; biopsy and lab testing on
tissue; presence/absence of receptors ER, PR, HER2
150
Breast cancer: Prevention
Have regular mammogram (free from 45 - 69 yrs)
Self examination of breast
Lifestyle - healthy weight, physical activity, quit smoking etc
151
Breast cancer:Treatment
Surgery, radiation, chemotherapy
Presence or absence of ER, PR and HER2 receptors determine best treatment
Trastuzumab (Herceptin) – monoclonal antibody that blocks HER2
Hormone treatment – block hormone receptors or lower hormone levels
-Tamoxifen – blocks ER in ER+ tumours
-Letrozole inhibits oestrogen production in peripheral tissues (post - menopause)
152
Skin Cancer:Incidence
NZ has highest rate in the world
Melanoma ~ 2,000 per year with ~ 350 deaths
Non-melanoma ~ 67,000 per year with ~ 130 deaths
153
Skin Cancer: Risk factors
```
Family history
Skin that burns easily
Cumulative sun exposure (age) or episodes
of severe sunburn, esp. as a child
Sunbeds
Less common
-X-ray exposure, scars from burns or disease,
exposure to some chemicals
```
154
Skin Cancer:Signs & symptoms
Red, scaly, rough skin lesions on sun-exposed
| areas; hands, head, neck, lips and ears
155
Skin Cancer:Diagnosis
Skin checks, mole maps
| Biopsy
156
Skin Cancer:Prevention
Cover skin, sunscreen, hats, sunglasses etc
| Check skin regularly including skin not normally exposed to sun
157
Skin Cancer:Treatment
```
Surgery
Cryotherapy – liq N2
5-fluoruracil cream
B-Raf inhibitors
Immunomodifiers (IFNα, IL-2, Ipilimumab)
Photodynamic therapy - photosensitiser drug and light or laser
treatment kills tumour cells with reactive oxygen species (ROS)
Radiation
```
158
Prostate cancer: Incidence
Second most frequently diagnosed cancer (15% of all male cancers)
>80% of men will develop prostate cancer by 80 yrs – mostly slow growing
159
Prostate cancer:Risk factors
Male > 50 yrs
Poor diet – obesity, link with red meat?
Family history, BRCA1/2
Elevated testosterone
160
Prostate cancer:Signs & symptoms
Initially asymptomatic
| Frequent urination, pain or difficulty with urination, blood in urine
161
Prostate cancer:Diagnosis
Digital rectal examination (DRE), ultrasound, MRI, biopsy
| Screening for prostate-specific antigen (PSA) – not clear if this is really useful
162
Prostate cancer:Prevention
Diet / exercise?
163
Prostate cancer:Treatment
Most are slow growing - managed with drugs to ↓ testosterone (Finasteride)
For aggressive tumours - surgery, radiation / brachytherapy, chemotherapy
164
Prostate cancer:Incidence
4th most common cancer in women worldwide
| 160 new cases in NZ each year and ~50 deaths
165
Prostate cancer:Risk factors
HPV greatest risk factor (mostly subtypes 16 & 18)
Number of sexual partners
Family history, smoking, poor diet
166
Prostate cancer:Signs & symptoms
Abnormal vaginal bleeding or discharge
| Tiredness, pain in pelvic area, legs or lower back
167
Prostate cancer:Prevention
Cervical screening using Papanicolaou (Pap) or smear test – every 3 years
HPV vaccination
Barrier protection during intercourse
168
Prostate cancer:Diagnosis
```
Pap test, visual inspection (colposcopy), and biopsy
Also imaging (ultrasound, CT, MRI, PET, bone scan)
```
169
Prostate cancer:Treatment
Surgery, radiation / brachytherapy, chemotherapy
