Cancer

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Cancer
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What is cancer?

• Uncontrolled growth and spread of abnormal cells
• Death occurs when vital passages are blocked,
  preventing oxygen and nutrients from being
  delivered
  
• Any one of 100 types of tumors

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Terms

• Neoplasm an abnormal tissue that grows by
  cellular growth more rapidly than normal and
  continues to grow after the stimuli that
  initiated the new growth ceases
• Benign noncancerous, encapsulated
• Malignant invades surrounding tissues and can
  spread

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• Since the 50s heart disease deaths have fallen by
  60
  
• In the 90s cancer deaths fell by 7
• Most of this is due to reduce cigarette use,
  improved early detection and treatment
  
• is expected to continue at 2 per year

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2000 Leading causes of death
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Individual risk

• ACS estimates lifetime risk of developing cancer
  is 44 for males and 38 for females
  
• 1,500 cancer deaths per day in US
• 60 5 year survival rate

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Lifetime probability of developing cancer
excluding skin cancer
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What about skin cancer?

• The probability of developing skin cancer in
  one's lifetime is one in five.
  
• Nearly 50 percent of all Americans age 65 or over
  will develop skin cancer at least once during
  their lifetime.
  
• Melanoma risk is 1 in 100.

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What is the connection between diet and cancer?

• 30-40 of all cancers are believed to be caused
  by an American diet
  
• Increasing consumption from 2 servings of fruits
  and vegetables to 5/day will cut the risk of many
  cancers in half
  
• Eating a plant based diet will dramatically
  reduce cancer incidence

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Added sugar and sugar rich foods in relation to
colorectal cancer
Relative risk
gr/day
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Oesophageal cancer and alcohol intake
Relative risk
Alcohol grams/day
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Lung cancer and vegetable intake
Relative risk
Vegetable intake grams/day
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Stomach cancer and vegetable intake
Relative risk
Vegetable intake grams/day
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Stomach cancer and fruit intake
Relative risk
Fruit intake grams/day
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Prostate Cancer and Fat Consumption
Sweden
Norway
USA
Canada
Australia
France
Austria
Canada
Germany
Portugal
Hungary
Ireland
Spain
Italy
Venezuela
Czechoslovakia
Death per 100,000
Romania
Israel
Panama
Poland
Bulgaria
Yugoslavia
Columbia
Greece
Mexico
Japan
Philippines
El Salvador
Advances in Cancer Research, 32237, 1980
Fat Consumption (gr/day)
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Colon Cancer and Fat Consumption
Denmark
Austria
Germany
Belgium
USA
Ireland
France
England
Switzerland
Italy
New Zealand
Netherlands
Australia
Norway
Canada
Israel
Death per 100,000
Greece
Japan
Finland
Singapore
Hong Kong
Important Advances in Oncology 1987.
Philadelphia
JB Lippincott Co 1987197-220
Fat Consumption (gr/day)
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Total Mammary Tumors in Rats
No. of Tumors
Antimutagenesis and Anticarcinogenesis
Mechanisms III. New York Plenum Press 199345
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Causes of cancer

• Environmental factors tobacco use, diet, and
  infectious diseases, as well as chemicals and
  radiation cause an estimated 75 of all cancer
  cases in the United States.
• Research shows that about 33-40of all cancer
  deaths are related to dietary factors
  
• 31 due to tobacco use
• What about physical activity?

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The Cancer Process
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Spontaneous or inherited mutation
Abnormal cell
Normal cell
Active carcinogen
Detoxified carcinogen
A carcinogen can be any substance that can alt
er the genetic make-up
of a cell
Inactive carcinogen
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Spontaneous or inherited mutation
Abnormal cell
Normal cell
Repair
Activated carcinogen
Detoxified carcinogen
Inactive carcinogen
Cell proliferation
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Spontaneous or inherited mutation
Abnormal cell
Normal cell
Repair
Activated carcinogen
Detoxified carcinogen
Inactive carcinogen
Tumor
Metastasis
Cell proliferation
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• How long does this entire process take?

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Cancer deaths by age, in 2001
80 of all cancers occur after age 55
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• How does over nutrition or estrogen relate to
  this process?

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Spontaneous or inherited mutation
Abnormal cell
Normal cell
Repair
Activated carcinogen
Detoxified carcinogen
Inactive carcinogen
Tumor
Metastasis
Cell proliferation
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• What does this model suggest regarding the
  benefits of preventing vs treating cancer?
  

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Five year survival rates by cancer site
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Cancer risk factors

• Diet
• Tobacco use
• Alcohol use
• Reproductive factors (breast feeding)
• Unsafe sex
• Environmental factors (sunlight, radiation,
  radon, air pollution)
  
• Family history of cancer
• Physical inactivity and obesity

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Spontaneous or inherited mutation
Abnormal cell
Normal cell
Repair
Activated carcinogen
Detoxified carcinogen
Inactive carcinogen
Tumor
Metastasis
Cell proliferation
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• How does the relationship between physical
  activity and colon cancer fit into this model?
  

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Spontaneous or inherited mutation
Abnormal cell
Normal cell
Repair
Activated carcinogen
Detoxified carcinogen
Inactive carcinogen
Tumor
Metastasis
Cell proliferation
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• Where do antioxidants fit in this model?

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Spontaneous or inherited mutation
Abnormal cell
Normal cell
Repair
Activated carcinogen
Detoxified carcinogen
Inactive carcinogen
Tumor
Metastasis
Cell proliferation
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The battle rages

• Free radicals
• VS
• Antioxidants/phytochemicals

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Free Radicals

• Any atom with a single electron in its outmost
  bonding orbital
  
• Oxygen has a high affinity for electrons, when it
  loses one oxygen it becomes an aggressive free
  radical (reactive oxygen species, ROS)

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Unpaired Electrons
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• Free radicals are unstable and begin to look for
  another atom from which it can obtain another
  electron
  
• Chain-reaction can cause 1,000s of atoms or
  molecules to be changed which can
  
• Disrupt or destroy cells
• Damage DNA, lipid membranes, mitochondria, and
  proteins
  
• Disrupt vital functions

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..
Ribosome
Serum albumin
Collagen
RNA
Free Radical Species
Ferritin
Penicillin binding protein
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Free radicals can

• Attach to other molecules and form bonds
• Give up their extra electron to another molecule
• Take electrons from another molecule
• Take away an atom of hydrogen rather that just
  one electron
  

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Where do free radicals come from?

• Most are produced by our own bodies by the
  electron transport system (ETC)
  

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Where do free radicals come from?

• UV light
• burned food
• toxic chemicals
• Industrial
• automobile pollution
• Unknown sources

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Cigarette Smoke

• One of the largest sources of free radicals
• One puff of smoke contains
• 100,000,000,000,000,000 free radical species
• Tobacco is responsible for 31 of all cancers

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Cancer death and smoking
Relative risk
Number of cigarettes/day
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How do we protect ourselves?

• Enzymatic protection enzymes in every cell help
  neutralize some free radicals. These include
  superoxide dismutase (SOD), catalase, and
  glutathione peroxidase.
• Proteins and compounds that bind with metal ions
  and keep them from creating other radicals, this
  process is called chelation (key-late-shun).
  

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Antioxidants (free radical scavengers)

• Able to donate electrons or hydrogen ions without
  having to replace it
  
• Vitamins C and E
• Phytochemicals (health promoting plant
  chemicals)
  
• React with radical species
• Dont become radicals themselves

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Phytochemicals

• Carotenoids
• Beta-carotene
• Lycopene
• Lutein
• Zeaxanthin
• Organosulfurs
• Flavinoids

• Phytosterols
• Alkaloids
• Tannins
• Saponins

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The process of cell damage
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• DNA in each cell gets a hit from a free radical
  every 10 seconds
  
• Each cell gets 10,000 hits/day

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Spontaneous or inherited mutation
Abnormal cell
Normal cell
Repair
Activated carcinogen
Detoxified carcinogen
Inactive carcinogen
Tumor
Metastasis
Cell proliferation
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Spontaneous or inherited mutation
Abnormal cell
Normal cell
Repair
Activated carcinogen
Detoxified carcinogen
Inactive carcinogen
Tumor
Metastasis
Cell proliferation
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Lycopene and other phytochemicals

• 72 studies of tomatoes and tomato products and
  cancer
  
• None showed an increase of risk
• Lower cancer risk for a variety of anatomical
  sites is associated with increased consumption of
  tomatoes and tomato products

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Lycopene and Cancer Death Relative Risk
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• Prostate Carcinogenesis in N-methyl-N-nitrosourea
  (NMU)-Testosterone-Treated Rats Fed Tomato
  Powder, Lycopene, or Energy-Restricted Diets
  
• Thomas W.-M. Boileau, Zhiming Liao, Sunny Kim,
  Stanley Lemeshow, John W. Erdman, Jr., Steven K.
  Clinton
  
• Affiliations of authors Division of Nutritional
  Sciences, University of Illinois,
  Urbana-Champaign, IL (TWMB, JWE) Division of
  Hematology and Oncology, Department of Internal
  Medicine, James Cancer Hospital and Solove
  Research Institute (ZL, SKC), School of Public
  Health (SL), Center for Biostatistics (SK), and
  Department of Human Nutrition (SKC), The Ohio
  State University, Columbus, OH.
• Correspondence to Steven K. Clinton, MD, PhD,
  A434 Starling Loving Hall, 320 West 10th Ave.,
  The Ohio State University, Columbus, OH 43210
  (e-mail clinton-1_at_medctr.osu.edu).
• Background Consumption of tomato products or
  lycopene and energy restriction have been
  hypothesized to reduce the risk of human prostate
  cancer. We investigated the effects of these
  dietary variables in a rat model of prostate
  carcinogenesis. Methods Male rats (n 194)
  treated with N-methyl-N-nitrosourea and
  testosterone to induce prostate cancer were fed
  diets containing whole tomato powder (13 mg
  lycopene/kg diet), lycopene beadlets (161 mg
  lycopene/kg diet), or control beadlets. Rats in
  each group were randomly assigned to either ad
  libitum feeding or 20 diet restriction.
  Differences between Kaplan-Meier survival curves
  for diet composition or restriction were tested
  with the log-rank test. Cox proportional hazards
  models were developed to examine the combined
  effect of diet composition and restriction on
  survival. Statistical tests were two-sided.
  Results Risk of death with prostate cancer was
  lower for rats fed the tomato powder diet than
  for rats fed control beadlets (hazard ratio HR
  0.74, 95 confidence interval CI 0.59 to
  0.93 P .009). In contrast, prostate
  cancer-specific mortality of the control and
  lycopene-fed rats was similar (P .63). The
  proportions of rats dying with prostate cancer in
  the control, lycopene, and tomato powder groups
  were 80 (95 CI 68 to 89), 72 (95 CI 60
  to 83), and 62 (95 CI 48 to 75),
  respectively. Rats in the diet-restricted group
  experienced longer prostate cancer-free survival
  than rats in the ad libitum-fed group (HR 0.68,
  95 CI 0.49 to 0.96 P .029). The proportion
  of rats that developed prostate cancer was 79
  (95 CI 69 to 86) for ad libitum-fed rats and
  65 (95 CI 54 to 74) for rats fed restricted
  diets. No interactions were observed between diet
  composition and dietary restriction. Conclusions
  Consumption of tomato powder but not lycopene
  inhibited prostate carcinogenesis, suggesting
  that tomato products contain compounds in
  addition to lycopene that modify prostate
  carcinogenesis. Diet restriction also reduced the
  risk of prostate cancer. Tomato phytochemicals
  and diet restriction may act by independent
  mechanisms. Journal of the National Cancer
  Institute, Vol. 95, No. 21, 1578-1586, November
  5, 2003

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Aging

• One theory of aging suggest that many of the
  changes that occur with aging are actually due to
  free radical cell damage and replacement
  
• What changes occur due to aging?

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What changes occur due to aging?

• wrinkles
• grey hair
• poor eyesight, hearing
• joint wear and tear
• sagging