Cancer Prevention and Screening

What is cancer caused by?

acquired DNA damage due to aetiological agents

examples of biological aetiological agents

• infections (e.g. HPV)

• inflammation (e.g. pancreatic cancer caused by chronic pancreatitis)

• chance (cell division or oxidative stress)

• inherited predisposition (retinoblastoma RB1, breast cancer BRCA1)

examples of chemical aetiological agents

• tobacco

examples of physical aetiological agents

• radiation (e.g. radon gas)

What is the carcinogenic agent implicated in the causation of scrotal carcinomas?

chimney smoke condensates

What is the carcinogenic agent implicated in the causation of mesothelioma?

asbestos

What is the carcinogenic agent implicated in the causation of oral carcinoma?

snuff

What is the carcinogenic agent implicated in the causation of nasal adenocarcinoma?

hardwood dust

What percentage of cancer deaths are caused by smoking?

30-40%

How does smoking cause cancer?

damages DNA

How is obesity linked to cancer?

Fat tissues in the body:

• increase inflammation

• increase oestrogen levels (major RF for breast cancer)

• produce hormones and growth factors 

Give three ways that infection can cause cancer

1. Transmissible cells

2. Viruses

3. Bacteria

How can transmissible cells cause cancer?

Tasmanian devils

Physical transfer of living cancer cells through biting or grooming

Viruses cause 10-15% of cancers. Give examples of human DNA viruses that are linked to cancer.

• Hep B virus (HBV) → hepatocellular carcinoma

• Human papilloma virus (HPV) → cervical cancer

• Kaposi’s sarcoma associated herpesvirus (KSHV) → Kaposi’s sarcoma

• Epstein-Barr virus (EBV) → Burkitt’s lymphoma, B/T cell lymphoma, Hodgkin’s lymphoma

Viruses cause 10-15% of cancers. Give examples of human RNA viruses that are linked to cancer.

• Hepatitis C virus (HCV) → hepatocellular carcinoma

• Human T-cell lymphotropic virus (HTLV-1) → Type 1 associated T-cell leukaemia

What is the only retrovirus known to directly cause cancer in humans?

human T-cell lymphotropic virus (HTLV-1)

human T-cell lymphotropic virus (HTLV-1)

HTLV-1 is a virus that causes a form of blood cancer called adult T-cell leukemia/lymphoma (ATL). The virus infects T cells, a type of white blood cell, and in a small percentage of infected individuals, this can lead to ATL, an aggressive and often fatal malignancy.

How do viruses cause cancer?

• insert DNA into host DNA (Hep B→ liver ca) (HPV → cervical ca)

• viral proteins inactivate important host proteins 

HPV E6 inactivates which host protein?

TP53 (tumour suppressor)

HPV E7 inactivates which host protein?

RB1

How is the immune system linked to cancer?

How can cancer risk be reduced?

• no smoking

• maintaining healthy body weight

• cutting back on alcohol

• balanced diet

• staying safe in the sun

• occupation

• avoiding infections (Hep B/HPV vaccination)

• screening programmes

• low dose aspirin

The NHS currently screens for which three cancers?

1. Breast (mammogram)

2. Bowel (FIT)

3. Cervical (HPV molecular)

What percentage of deaths are due to metastatic cancer?

90%

tumour definition

• abnormal mass of tissue that results from excessive cell division that is uncontrolled and progressive

• can be benign or malignant

• “swelling”, not necessarily a neoplasm

neoplasia

differentiation

extent to which neoplastic cells resemble normal cells

• well

• moderately

• poorly

anaplasia

lack of differentiation 

considered hallmark of malignancy

pleomorphism

variation in cell/nuclear size and shape

dysplasia

disordered growth, loss of uniformity and loss or architectural orientation

Unlike cancer, hyperplasia, hypertrophy and metaplasia are reversible upon the removal of the inducing stimulus. What is hyperplasia?

increase in number of cells 

Unlike cancer, hyperplasia, hypertrophy and metaplasia are reversible upon the removal of the inducing stimulus. What is hypertrophy?

increase in size of cells

Unlike cancer, hyperplasia, hypertrophy and metaplasia are reversible upon the removal of the inducing stimulus. What is metaplasia?

where one adult cell type is replace by another cell type

e.g. columnar to squamous in respiratory tracts of smokers due to chronic irritation (precursor to neoplasia if irritation persists)