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Cancer

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Diet restriction also reduced the risk of prostate cancer. Tomato phytochemicals and diet restriction may act by independent mechanisms. ... – PowerPoint PPT presentation

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Title: Cancer


1
Cancer
2
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

3
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
9
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

10
Lifetime probability of developing cancer
excluding skin cancer
11
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

14
Added sugar and sugar rich foods in relation to
colorectal cancer
Relative risk
gr/day
15
Oesophageal cancer and alcohol intake
Relative risk
Alcohol grams/day
16
Lung cancer and vegetable intake
Relative risk
Vegetable intake grams/day
17
Stomach cancer and vegetable intake
Relative risk
Vegetable intake grams/day
18
Stomach cancer and fruit intake
Relative risk
Fruit intake grams/day
19
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)
20
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)
21
Total Mammary Tumors in Rats
No. of Tumors
Antimutagenesis and Anticarcinogenesis
Mechanisms III. New York Plenum Press 199345
22
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?

23
The Cancer Process
24
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
25
Spontaneous or inherited mutation
Abnormal cell
Normal cell
Repair
Activated carcinogen
Detoxified carcinogen
Inactive carcinogen
Cell proliferation
26
Spontaneous or inherited mutation
Abnormal cell
Normal cell
Repair
Activated carcinogen
Detoxified carcinogen
Inactive carcinogen
Tumor
Metastasis
Cell proliferation
27
  • How long does this entire process take?

28
Cancer deaths by age, in 2001
80 of all cancers occur after age 55
29
  • How does over nutrition or estrogen relate to
    this process?

30
Spontaneous or inherited mutation
Abnormal cell
Normal cell
Repair
Activated carcinogen
Detoxified carcinogen
Inactive carcinogen
Tumor
Metastasis
Cell proliferation
31
  • What does this model suggest regarding the
    benefits of preventing vs treating cancer?

32
Five year survival rates by cancer site
33
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

34
Spontaneous or inherited mutation
Abnormal cell
Normal cell
Repair
Activated carcinogen
Detoxified carcinogen
Inactive carcinogen
Tumor
Metastasis
Cell proliferation
35
  • How does the relationship between physical
    activity and colon cancer fit into this model?

36
Spontaneous or inherited mutation
Abnormal cell
Normal cell
Repair
Activated carcinogen
Detoxified carcinogen
Inactive carcinogen
Tumor
Metastasis
Cell proliferation
37
  • Where do antioxidants fit in this model?

38
Spontaneous or inherited mutation
Abnormal cell
Normal cell
Repair
Activated carcinogen
Detoxified carcinogen
Inactive carcinogen
Tumor
Metastasis
Cell proliferation
39
The battle rages
  • Free radicals
  • VS
  • Antioxidants/phytochemicals

40
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)

41
Unpaired Electrons
42
  • 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

43
..
Ribosome
Serum albumin
Collagen
RNA
Free Radical Species
Ferritin
Penicillin binding protein
44
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

45
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

48
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

49
Cancer death and smoking
Relative risk
Number of cigarettes/day
50
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).

51
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

52
Phytochemicals
  • Carotenoids
  • Beta-carotene
  • Lycopene
  • Lutein
  • Zeaxanthin
  • Organosulfurs
  • Flavinoids
  • Phytosterols
  • Alkaloids
  • Tannins
  • Saponins

53
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

59
Spontaneous or inherited mutation
Abnormal cell
Normal cell
Repair
Activated carcinogen
Detoxified carcinogen
Inactive carcinogen
Tumor
Metastasis
Cell proliferation
60
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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64
  • 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

65
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?

66
What changes occur due to aging?
  • wrinkles
  • grey hair
  • poor eyesight, hearing
  • joint wear and tear
  • sagging
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