Todays topics

1
Todays topics

• Epidemiology
• Role of chemicals and physical agents in cancer
• Role of infectious agents in cancer
• Oncogenes

2
Epidemiology

• The study of large cohorts to analyze trends in
  output this can indicate factors that promote
  cancer progression

3
US Mortality, 2001
No. of deaths
of all deaths
Rank
Cause of Death

• 1. Heart Diseases 700,142 29.0
• 2. Cancer 553,768 22.9
• 3. Cerebrovascular diseases 163,538 6.8
• 4. Chronic lower respiratory diseases 123,013
  5.1
• 5. Accidents (Unintentional injuries) 101,537
  4.2
• 6. Diabetes mellitus 71,372 3.0
• 7. Influenza and Pneumonia 62,034 2.6
• 8. Alzheimers disease 53,852 2.2
• Nephritis 39,480 1.6

Source US Mortality Public Use Data Tape 2001,
National Center for Health Statistics, Centers
for Disease Control and Prevention, 2003.
4
Change in the US Death Rates by Cause, 1950
2001
Rate Per 100,000
1950 2001
HeartDiseases
CerebrovascularDiseases
Pneumonia/Influenza
Cancer
Age-adjusted to 2000 US standard
population. Sources 1950 Mortality Data -
CDC/NCHS, NVSS, Mortality Revised. 2001 Mortality
DataNVSR-Death Final Data 2001Volume 52, No. 3.
http//www.cdc.gov/nchs/data/nvsr/nvsr52/nvsr52_03
.pdf
5
2004 Estimated US Cancer Deaths
Men290,890
Women272,810

• 25 Lung bronchus
• 15 Breast
• 10 Colon rectum
• 6 Ovary
• 6 Pancreas
• 4 Leukemia
• 3 Non-Hodgkin lymphoma
• 3 Uterine corpus
• 2 Multiple myeloma
• 2 Brain/ONS
• 24 All other sites

Lung bronchus 32 Prostate 10 Colon
rectum 10 Pancreas 5 Leukemia 5 Non-Hodgkin 4
lymphoma Esophagus 4 Liver intrahepatic 3bil
e duct Urinary bladder 3 Kidney 3 All other
sites 21
ONSOther nervous system. Source American Cancer
Society, 2004.
6
Cancer Death Rates, for Men, US, 1930-1999
Rate Per 100,000
Lung
Prostate
Stomach
Colon and rectum
Pancreas
Leukemia
Liver
Age-adjusted to the 2000 US standard
population. Source US Mortality Public Use Data
Tapes 1960-1999, US Mortality Volumes 1930-1959,
National Center for Health
Statistics, Centers for Disease Control and
Prevention, 2002.
7
Cancer Death Rates, for Women, US, 1930-1999
Rate Per 100,000
Lung
Uterus
Breast
Colon and rectum
Stomach
Ovary
Pancreas
Age-adjusted to the 2000 US standard
population. Source US Mortality Public Use Data
Tapes 1960-1999, US Mortality Volumes 1930-1959,
National Center for Health
Statistics, Centers for Disease Control and
Prevention, 2002.
8
Tobacco Use in the US, 1900-1999
Per capita cigarette consumption
Male lung cancer death rate
Female lung cancer death rate
Age-adjusted to 2000 US standard
population. Source Death rates US Mortality
Public Use Tapes, 1960-1999, US Mortality
Volumes, 1930-1959, National Center for Health
Statistics, Centers for Disease Control and
Prevention, 2001. Cigarette consumption Us
Department of Agriculture, 1900-1999.
9
What is Cancer?

• lt1970s an infection or a disease of self?
• 2 opposing camps
• Cancer is caused by chemical and physical agents
• Cancer is caused by infectious agents

10
Early population studies

• English chimney sweeps
• Developed scrotal cancer
• Women who painted luminescent radium on
  wristwatches
• Developed tongue cancer

External factors can influence cancer
11
If outside factors can cause cancer, can it be
mimicked in the lab?

• Many tried, many failed
• Katsusaburo Yamagiwa repeated, prolonged
  exposure seemed to be necessary painted coal tar
  on rabbits ears rabbits developed skin cancer.
• X-rays also caused cancer technicians
  frequently contracted skin tumors and leukemia
• What could X-rays and chemicals possibly have in
  common?

12
Genes

• Herman Muller discovered that fruit flies exposed
  to X-rays could be mutated and transmit the
  mutation to offspring
• X-rays could mutate genes
• Similar experiments with chemicals such as
  mustard gas gave same results
• Chemicals could mutate genes
• Carcinogens are really mutagens and this is the
  cause of cancer

13
Infectious disease

• Peyton Rous (Nobel Prize, 1966 for the discovery
  of oncoviruses) Rous Sarcoma Virus
• Follows Kochs postulates, can purify from one
  animal (chicken), reinfect, and cause new tumor
  to form.

14
Viruses

• Viral life span simple genetic organism
  encapsulated in protein and lipid, only lives to
  replicate itself, no signals or concern from
  outside environment
• Multiple avian and mouse viruses were identified
  and followed Kochs postulates
• Cancer is caused by viruses
• But epidemiologically, didnt fit an infectious
  disease. All people carried latent forms of
  these viruses, but some special event activates
  them

15
Pretty good evidence for both of these theories..

• But the answer finally came from the study of
  viruses.

16

• Varmus and Bishop (Nobel prize 1989 for the
  discovery of the cellular origin of retroviral
  oncogenes)
• Using RSV, discovered the first oncogene, Src
• Upon using hybridization experiments, discovered
  the presence of this gene in all metazoans, from
  nematodes to humans.
• Cancer is a disease of self

Subsequently, many oncogenes have been identified
as both viral genes and by other mechanisms
17
If its not the viral infection causing cancer,
then what is? How do Retroviruses replicate?
18
The capture of protooncogenes by retroviruses.
19
What is the cause of cancer? Cancer is caused by
genetic disregulation

• Mutagens
• chemicals
• radiation
• Anything that can mutate genes

• Viruses
• Retroviruses
• Anything that can alter the function of genes

Key mediator in human cancer random mutations
20
(No Transcript)
21
(No Transcript)
22
(No Transcript)
23
Todays topics

• Epidemiology
• Role of chemicals and physical agents in cancer
• Role of infectious agents in cancer
• Oncogenes

24
(No Transcript)