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FNH 477 > Cancer > Flashcards

Cancer Flashcards

1
Q

Comment on current trends in cancer incidence in Canada.

A
  • Cancer is the #1 leading cause of death in Canada
  • 2 in 5 Canadians will develop cancer in their lifetime
  • 1 in 4 will die from cancer
  • 5-year survival is ~64%
  • Most common cancer in men is prostate
  • Most common cancer in women is breast
  • 2nd most common for both is lung and bronchus
  • 3rd most common for both is colorectal
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2
Q

What is cancer?

A
  • Uncontrolled cell growth (genetic mutations; epigenetic alterations in gene transcription)
  • Spread of abnormal cells throughout the body (metastasis)
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3
Q

Comment on liver disease incidence in Canadians.

A
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4
Q

Describe the general
stages of cancer progression

A
  • Initiation: ranges from minutes to days (short duration); cancer causing agent; no DNA repair, impaired regulation of apoptosis
  • Promotion: may last months or even years; altered DNA leads to changes in gene expression, protein function etc; cell proliferates in uncontrolled way; alcohol, estrogen in breast tissue, Helicobacter pylori in the stomach, HPV in cervix may act as promoters
  • Progression: malignant cells invade surrounding tissue and metastasize
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5
Q

Give examples of factors that may promote cancer. [4]

A
  • Alcohol
  • Estrogen in breast tissue
  • Helicobacter pylori in the stomach
  • HPV in cervix
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6
Q

Give examples of factors that may initiate cancer. [3]

A
  • Chemicals
  • Radiation (e.g., from the sun)
  • Viruses
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7
Q

‘Cancer’ can refer to either a benign or malignant tumor.
True or False?

A

False.
Cancer only refers to malignant tumors.

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8
Q

‘Cancer’ only refers to malignant tumors, but not benign tumors.
True or False?

A

True.

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9
Q

‘Cancer’ only refers to benign tumors, but not malignant tumors.
True or False?

A

False.
Cancer refers to malignant tumors only.

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10
Q

Compare malignant and benign tumors.

A
  • Benign (not cancer) tumor cells grow only locally and cannot spread by invasion or metastasis.
  • Malignant (cancer) tumor cells invade neighbouring tissues, enter blood vessels, and metastasize to different sites.
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11
Q
A

Answer: B
These genes specifically are responsible to recognize that the cell is modified. When modifications are detected the cell is directed to repair and cannot undergo division.

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12
Q

Compare tumor supressor genes and oncogenes.

A

Tumor-suppressor: protect against cancer
Oncogenes: drive cancer development

In cancer, inhibition of tumour suppression and activation of oncogenes.
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13
Q

Describe molecular changes in cancer. [5]

A
  • Inhibition of tumor suppressor genes
  • Activation of oncogenes
  • Changes in signal transduction pathways
  • Chromosomal rearrangements
  • Genome instability

This all leads to uncontrolled cell growth and migration.

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14
Q

Give examples of genetic alterations that may lead to carcinogenesis. [3]

A
  • Point mutations
  • Polymorphisms
  • Copy number variants

However, genetic predisposition may only account for 5-10% of risk.

For example, BRCA1 and BRCA2

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15
Q

Describe BRCA1 and BRCA2 mutations.

A
  • Missing protein; non-functional
  • Defective:
    • DNA repair
    • Transcription
    • G2/M cell cycle checkpoint regulation
    • Spindle checkpoint
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16
Q

How do we know factors other
than genetics contribute to cancer
risk?

A
  • Japanese families that move to the US exhibit different cancer risk than Japanese families living in Japan.
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17
Q

Describe epigenetic changes that may lead to carcinogenesis. [3]

A
  • DNA methylation
  • Histone covalent modifications
  • microRNAs
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18
Q

What is epigenetics?

A

“The study of heritable changes in the phenotype or gene expression caused by mechanisms other than changes in DNA sequences”

In genetics, gene sequence changes; in epigenetics, expression of genes changes = can lead to same outcome.

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19
Q

What are the three components of the epigenome?

A
  • DNA methylation
  • Histone modifications
  • non-coding microRNA
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20
Q

What is DNA methylation?

A
  • Refers to attachments of a methyl group to a cytosine group on DNA
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21
Q

Describe the effect of DNA methylation on gene activity.

A

Hypermethylation: silencing
Hypomethylation: activation

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22
Q

How is the landscape of DNA methylation visualized?

A

Oncogenes lose methylation (become activated); tumor suppressor genes gain methylation (become silenced)

This is an example in liver cancer.
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23
Q

How does nutrition impact the epigenome?

A

SAM, a methyl donor, requires micronutrients for de novo synthesis. Lack of these nutrients means that methylation cannot occur as normal.

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24
Q

List some bioactive compounds in vegetables and spices.

A

These impact the epigenome and therefore how the body functions.

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25
Q

What are the functional benefits of nutritional epigenetic effects? [6]

A
  • Decrease in cell proliferation
  • Decrease in cell migratory and invasive properties
  • Inhibition of oncogenic signalling pathways
  • Anti-oxidant role to prevent oxidative DNA damage
  • Activation of pathways for detoxifying potential carcinogens
  • Decrease in inflammatory response
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26
Q

What are most cancers related to?

A
  • 80-90% of cancers are related to environmental factors (e.g., chemicals, radiation, viruses/bacteria, carcinogens in food, “poor diet”)
  • These factors modify the structure and function of DNA leading to epigenetic aberrations
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27
Q

Give three examples of carcinogens in food.

Carcinogen = capable of causing cancer

A
  • Nitrosamines
  • Heterocyclic amines
  • Polycyclic aromatic hydrocarbons
28
Q

List aspects of diet that may be related to cancer.

A
  • Energy balance, growth rates & body size
  • Fat intake
  • Processed or red meat
  • Dairy
  • Fiber
  • Alcohol
  • Fruits and vegetables
  • Vitamins and minerals

This list is not exhaustive.

29
Q

Body fatness is associated with increased risk of breast cancer in postmenopausal women, but may be associated with decreased risk of breast cancer in premenopausal women. In this case, menopausal status is a(n):

A

Effect modifier
Modifies a relationship that likely exists but does not explain it.

30
Q

What is a secondary outcome?

A

A secondary outcome is used to evaluate additional effects of the intervention, additional events of interest, but which the study is not specifically powered to assess (e.g., primary outcome – liver cancer, secondary outcome – HBV-related liver cancer).

31
Q

What is a dependent variable?

A

The values of dependent variables (outcome variable) depend on the values of independent variable (exposure variable).

E.g., Independent variable is the dose of a drug; dependent variable is the frequency/intensity of symptoms upon different doses.

32
Q

What is a confounder?

A

A confounder influences both the dependent variable (outcome) and independent variable (exposure) causing an association-like appearance.

33
Q

What is an effect modifier?

A

An effect modifier modifies the relationship between the exposure and the outcome (but does not explain it).

34
Q

What is an intervening variable?

A

An intervening variable is a hypothetical variable used to explain causal links between exposure and outcome.

E.g., being poor and having a shorter life span: lack of access to healthcare or poor nutrition could be the intervening variables.

35
Q

Discuss body fatness and weight gain and cancer risk.

A
  • Obesity (body fatness) positively associated with cancer of colorectum, kidney, pancreas, esophagus, liver, endometrium, and breast (postmenopausal)
36
Q

Discuss physical activity and cancer.

A
  • Convincing evidence that physical activity decreases risk of colon cancer (probable evidence for other cancers)
37
Q

Discuss red & processed meat and cancer.

A
  • Convincing evidence that processed meat increases risk of colorectal cancer
  • Probable evidence that red meat increases risk of colorectal cancer and nasopharynx cancer
  • Processed meat group 1 = Carcinogenic
  • Red meat Group 2A = Probably carcinogenic
38
Q

Describe dairy and fish and cancer.

A
  • Probable evidence that dairy products decreases risk of colorectal cancer
  • Evidence is only limited to suggest fish decreases risk of cancer
  • May be due to calcium, possibly vitamin D or other components of milk (e.g., polyunsaturated fatty acids)
39
Q

Describe dietary fibre and cancer.

A
  • Probable evidence that foods containing dietary fiber decrease risk of colorectal cancer
  • Possible mechanisms:
    • provides bulk to speed transit time
    • may bind carcinogens in gut
    • alters colonic flora
    • substrate for generation of short chain fatty acids, which may be protective
40
Q

Describe alcohol and cancer.

A
  • Convincing evidence that alcohol increases risk of mouth, pharynx, larynx, esophagus, liver, colorectal, and breast (post-menopausal) cancer
  • Probable evidence for stomach and breast (pre-menopausal) cancer
  • Mechanism:
    • Toxic effects
    • Anti-folate effects
Alcohol consumption is not recommended because no amount is safe. Even though there is evidence that low amounts of alcohol can protect against cardiovascular disease. There are too many risks associated with increasing alcohol consumption, so it is not safe to recommend. There are other, safer ways to reduce cardiovascular disease risk.
41
Q

Discuss vegetables and fruits and cancer.

A
  • Probable evidence that non-starchy vegetables and fruits decrease risk of aerodigestive cancers
  • Although the evidence for the link with individual cancers is limited, the pattern of association is consistent and in the same direction
  • Overall, the evidence is more persuasive of protective effects
42
Q

Give examples of vegetables and fruits that are of special interest regarding cancer risk. [5]

A
  • Dark green and orange vegetables
  • Cruciferous vegetables (sulforaphane)
  • Soy products (genistein)
  • Allium vegetables (organosulfides)
  • Red vegetables and fruits (lycopene, anthocyanins)
43
Q

Describe isolated dietary supplements of beta-carotene in individuals predisposed for lung cancer.

A
  • Convincing evidence that high dose beta-carotene supplements increase risk of lung cancer in people who smoke and used to smoke tobacco.
44
Q

Also describe what the other factors are, if not the confounder.

A
  • Genetics does not affect dairy consumption (exposure), though it may affect risk of cancer (outcome). This is an effect modifier.
  • Better nutrition knowledge affects both the exposure and the outcome; however cancer risk decreases because better nutrition knowledge means people will be consuming healthier diets overall. This is the confounding factor.
  • The type of cancer is a dependent variable (i.e., an outcome).
  • Vitamin D is a mediating variable. Milk contains vitamin D, and vitamin D reduces risk of colon cancer. The relationship that exists is between vitamin D and colon cancer. Note this is not the same thing as an intervening variable.
45
Q

What is the difference between an intervening variable and a mediating variable?

A
  • While both explain the causal relationship, an intervening variable is only hypothetical, whereas a mediating variable has defining mechanisms that are well studied and known. (e.g., vitamin D is a mediating variable explaining the relationship between milk and decreased colon cancer risk).
46
Q

Discuss vitamins & minerals and cancer risk.

A
  • Limited evidence that:
    • Foods containing beta-carotene and retinol decrease risk of lung cancer
    • Multivitamin supplements decrease risk of colorectal cancer
    • Vitamin D decreases risk of colorectal cancer
    • Selenium or vitamin E may decrease risk of prostate cancer
    • Foods containing vitamin C decrease risk of colorectal and lung (people who smoke) cancers
    • Diets high in calcium increase risk of prostate cancer
  • Probable evidence that calcium supplements decrease risk of colorectal cancer

The evidence discussed here is not an exhaustive list.

47
Q

Discuss dietary fat and cancer risk.

A
  • Evidence is limited and not conclusive.
    • Difficult to separate effects of fat intake from total energy intake.
    • Possible confounding effects (e.g., animal protein intake or other lifestyle factors)
    • Types of fat may be important (limited suggestive evidence for saturated fat and pancreatic cancer)
48
Q

Discuss sugars and sugary beverages and cancer risk.

A
  • Limited-suggestive evidence that foods and drinks containing fructose increase risk of pancreatic cancer
  • Limited evidence that foods and drinks containing fructose increase risk of colorectal, oesophageal, lung, gallbladder, breast, prostate, kidney and bladder cancer
49
Q
A
  • Low certainty
  • High benefit: risk
50
Q

Describe 8 recommendations for cancer prevention.

A
  • Be a healthy weight: keep weight within healthy range and avoid weight gain in adult life
  • Be physically active: as a part of every day life; walk more and sit less
  • Eat a diet rich in wholegrains, vegetables, fruit and legumes: make these foods a major part of usual daily diet
  • Do not use supplements for cancer prevention: aim to meet nutritional needs through diet alone
  • Limit consumption of ‘fast food’ and other processed foods high in fat, starches, or sugars: limiting these foods helps control calorie intake and maintain a healthy weight.
  • Limit consumption of red and processed meat: eat no more than moderate amounts of red meat; eat little, if any, processed meat.
  • Limit consumption of sugar sweetened beverages: drink mostly water and unsweetened drinks
  • Limit alcohol consumption: for cancer prevention, it’s best not to drink alcohol
51
Q

There is limited evidence that foods containing beta-carotene and retinol […]

A

There is limited evidence that foods containing beta-carotene and retinol decrease risk of lung cancer

52
Q

There is limited evidence that multivitamin supplements […]

A

There is limited evidence that multivitamin supplements decrease risk of colorectal cancer.

53
Q

There is limited evidence that vitamin D […]

A

There is limited evidence that vitamin D decreases risk of colorectal cancer.

54
Q

There is limited evidence that selenium or vitamin E may […]

A

There is limited evidence that selenium or vitamin E may decrease risk of prostate cancer

55
Q

There is limited evidence that foods containing vitamin C […]

A

There is limited evidence that foods containing vitamin C decrease risk of colorectal and lung (people who smoke) cancers

56
Q

There is limited evidence that diets high in calcium […]

A

There is limited evidence that diets high in calcium increase risk of prostate cancer.

57
Q

There is probable evidence that calcium supplements […]

A

There is probable evidence that calcium supplements decrease risk of colorectal cancer.

58
Q

There is probable evidence that alcohol […]

A

There is probable evidence that alcohol increases risk for stomach and breast cancer (pre-menopausal), and decreases risk of kidney cancer.

59
Q

There is probable evidence that whole grains […]

A

There is probable evidence that whole grains decrease risk of colorectal cancer.

60
Q

There is probable evidence that dietary fibre […]

A

There is probable evidence that dietary fibre decreases risk of colorectal cancer.

61
Q

There is probable evidence that non-starchy fruits and vegetables […]

A

There is probable evidence that non-starchy fruits and vegetables decrease risk of aerodigestive cancers.

62
Q

There is probable evidence that foods preserved with salt […]

A

There is probable evidence that foods preserved with salt increase risk of stomach cancer.

63
Q

There is convincing evidence that aflatoxins […]

A

There is convincing evidence that aflatoxins increase risk of liver cancer.

64
Q

There is probable evidence that low intake of non-starchy vegetables […]

A

There is probable evidence that low intake of non-starchy vegetables increase risk of colorectal cancer.

65
Q

There is probable evidence that low fruit intake […]

A

There is probable evidence that low fruit intake increase risk of colorectal and stomach cancer.

66
Q

There is probable evidence that preserved non-starchy vegetables […]

A

There is probable evidence that preserved non-starchy vegetables increase risk of nasopharynx cancer.

67
Q

What are 4 possible mechanisms for why dietary fibre decreases risk of colorectal cancer?

A
  • provides bulk to speed transit time
  • may bind carcinogens in gut
  • alters colonic flora
  • substrate for generation of short chain fatty acids, which may be protective

FNH 477 (11 decks)

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