Nutrition and Cancer Flashcards
What is the leading cause of death in developed countries?
Cancer
What suggests that cancer is largely environmental, and not genetic?
Differences in cancer prevalence worldwide, and changes in populations that migrate to western countries
Why does cancer develop? (3)
Due to interactions between genetic background, endogenous milieu and exogenous exposures
Why is a very important risk factor for cancer?
AGE - as cancer takes awhile to develop
Most prevalent type of cancer in men? Women?
Prostate, breast
What is the deadliest type of cancer in men? Women?
Lung
Define cancer
Uncontrolled growth abnormal cells in the body
Name some characteristics of cancerous cells
- Escape normal growth signals
- Can avoid programmed cell death
- Avoid immune surveillance,
- Can invade other tissues
- Develop angiogenesis
Synonyms of cancer?
Malignant tumors, neoplasms, carcinoma
(T/F) Benign tumors are cancerous
False -as the do not invade and mestastasize
What is carcinogenesis?
The process of cancer development (ONCE the cancer has developed)
What is the 3-step classical view of carcinogenesis?
- Initiation
- Promotion
- Progression
_____ will promote cell-growth and division
Proto-oncogenes
_____ will inhibit cell-growth and survival
Tumor suppressing genes
Explain the 3-step classical carcinogenesis
Begins with initiation, where there is a single cell with DNA damage, becoming a cancerous cell which will undergo proliferation and eventually form a mass –> Tumor
Is DNA damage normal?
Yes, but we have tumor suppressing genes which will inhibit cell-growth and survival
Explain the multi-stage modern view of carcinogenesis
The DNA damaged cell may mutate and proliferate, inactivating a DNA repair gene and change proto-oncogenes into oncogenes which will promote cell-growth and division –> ultimately by inhibiting tumor-suppressing genes, eventually leading to the formation of a cancerous mass.
In multi-stage carcinogenesis, what may there be defects in? What does it contribute to?
- Terminal differentiation
- Growth control
- Resistance to cytoxicity
- Programmed cell death
- -> Selective clonal expansion
In multi-stage carcinogenesis, what is activated? Inactivated? What does this contribute to?
- Activation of protooncogenes
- Inactivation of tumor-suppressor genes
- Inactivation of genomic stability genes
- –> Selective colonal expansion
Initiated cell —> Preneoplastic lesion is progressed by what?
Selective colonal expansion
Preneoplasti lesion —> Malignant tumor is progressed by what?
Genetic change
Malignant tumor –> Clinical cancer is progressed by what?
Genetic change
Clinical cancer –> ______
Cancer metastasis, through genetic change
There are strategies at ____ to prevent cancer
every step of the way
Anti-initiation strategies?
Limit the development of the first, altered cell.
Limit genetic and epigenetic alteration
Anti-initiation strategy mechanism? (4)
- Alter carcinogen metabolism
- Enhance carcinogen detoxification
- Scavenge electrophiles/ROS
- Enhance DNA repair
Anti-promotion/progression strategies?
Limit the initiated, DNA damaged cell to developing into the preneoplastic stage.
Limit and increases in cell proliferation, additional genetic and epigenetic alterations.
Anti-promotion/progression strategy mechanisms?
- Scavenge ROS
- Decrease inflammation
- Suppress proliferation
- Enhance apoptosis
- Enhance immunity
- Discourage angiogenesis
How can the expression of one gene (i.e. phenotype) be increased?
- Higher penetrance
- Epigenetic’s (environment, including nutrition)
the higher the penetrance, the ____ likelihood of the gene expressing it’s phenotype
greater
Define gene mutation
Structural change in the base pair sequence of DNA, may be inherited or due to exogenous factors
Which gene mutation is notable for increasing risk of beast and ovarian cancer? Why?
BRCA1 gene, high penetrance
Define polymorphisms
Structure of the gene varies amongst individuals, may or may not show phenotypes
(T/F) Polymorphisms are less common than gene mutations
FALSE - PM are more common
(T/F) Polymorphisms are more common than GM, but display LESS penetrance than GM
True
Example of polymorphisms?
SNP
What are SNPs?
Will affect response of genes to certain exposures, do NOT affect the reading of the gene
If an SNP is never exposed to _____ it may remain dormant
the right exposure
Define epigenetic changes
Affect gene structure, function and expression
Most common epigenetic changes?
DNA methrylation
What could cause the silencing of tumor suppressing genes, leading to increased cell growth and division?
DNA hypermethylation
What is a known epigenetic effect that could cause cancer cells to grow and proliferate?
DNA hypermethylation of tumor-suppressing genes
Define nutritional genomics and proteomics
The interaction between diet, genes and their products
(T/F) the greatest impact of bioactive food components is their direct effect on DNA
False, will impact more the epigenomic
What is the epigenomic?
Expression of mRNA and post-translational modifications of the protein
Knowing diet-gene interactions primarily impact the epigenome, how are proteins affected?
Structure of proteins, transport, enzymes and signalling by phosphorylation, glycosylation
How may bioactive food components directly impact DNA?
Oxidative damage to DNA from carcinogenic food products
What are the main possible causes of cancer?
-Tobacco, diet, obesity
What % does UV rays, pollution and professional exposure play in development of cancer?
Only 2-5% each, small
What do all the possible causes of cancer play on?
The individuals genetic variability
Dietary sources of carcinogens that may cause oxidative damage ?
- Oxidized PUFA, free iron, nitrosamines
- Glycophosphates from pesticides
Dietary components that may reduce oxidative damage?
Antioxidant nutrients (Vit C, E, A) or cofactors in antioxidant enzymes (selenium, copper)
What may regulate cell proliferation and differentiation?
Vitamins A and D, interact with promoter regions of many genes
Which nuclear receptors are activated by oxidized fats?
PPAR-alpha
What can affect gene expression in cell culture?
Catechins (green tea, apples, chocolate)
What should be considered about in-vitro studies?
When any cell is exposed to something new in-vitro, there will be an effect and should be replicate in animal models..
Examples of roles of bioactive food components on carcinogenesis?
- DNA repair
- Cell differentiation
- Hormone regulations
- Carcinogen metabolism
- Inflammatory response
- Apoptosis
- Cell growth cycle
Define incidence
New cases diagnosed
Define prevalence
All cases present at time of evaluation
Define mortality (cancer)
Number of cancer deaths, and related to each cancer.
Why are breast and prostate cancers more prevalent despite lunch and bronchus cancer being the highest cause of mortality?
Diagnosis and breast and prostate cancer is much easier, and can be made at an earlier stage.
Explain the diagnosis of prostate cancer
PCA protein measured through a simple, annual blood test and can be treated immediately
Explain the diagnosis of breast cancer
Self-breast examinations, and every 2 year mammographs for women over 50.
Diagnosis of lung cancer?
Much more harder to diagnose, as it is an internal organ and may not present symptoms, and typically picked up in a routine x-ray
Issue with lung cancer?
Even if diagnosed early, aggressive. Diagnoses are typically later
Describe our current population and how this relates to cancer incidence
Larger and agin population. Since we know the greatest risk factor for cancer is AGE, naturally we will have a higher incidence of cancer.
When adjusted for age and population growth, have incidences of cancer increased since 1987?
No
When adjusted for age, has incidence of cancer increased in men? Women?
Women remains the same, while men slightly declines
Trends in cancer mortality?
NUMBER of cancer has increased over time, and cancer remains the leading cause of mortality, however cancer mortality has DECREASED overall.
What may explain the decrease in cancer mortality from men?
Less smoking
Why has cancer mortality from smoking decreased?
Public health messages on smokin cessation
Why has lung cancer mortality increased for women after 1987?
In general, women started smoking after men
What is much more aggressive in pre-menopausal women?
Breast cancer (responsiveness to estrogens, which are mitogens)
Cancer mortalities 0-14?
- Brain/CNS
- Leukema
- Connective tissue
- Bone
- Kidney
Cancer mortalities 15-29?
- Brain/CNS
- Leukemia
- Bone
- CT
- Non-hodgkins lymphoma
- Colorectal
- Melanoma
Cancer mortalities 30-49?
- Breast
- Lung/bronchus
- Colorectal
- Brain/CNS
- Pancreas
Cancer mortality 50-69?
- Lung/bronchus
- Colorectal
- Breast
- Pancreas
- Prostate
Cancer mortality 70+?
- Lung/bronchus
- Colerectal
- Prostate
- Breast
- Pancreas
Countries w/ highest cancer incidence?
-Canada, US, Australia, UK, Western Europe, Uruguay
Cancers more prevalent in developed countries?
Lung, breast and prostate cancer
Cancers more prevalent in developing countries?
Liver (Hep C infections)
-Overall cancer incidence is lower in developing countries
What could explain differences in types and incidences of cancers amongst countries?
Different exposures and risk factors
Describe the nature of the dose-response relationship between diet and cancer
We must know the quantity of the nutrient or component of the food that must be consumed to seen effects on cancer - is this amount realistic/seen in normal diets?
Explain the temporal relationship between diet and cancer
If we are exposed to a certain diet or carcinogen throughout our life-time, how long will it take to develop cancer? Do we need continuous exposure?
List the type of studies addressing diet and cancer in increasing strength of association: Prospective co-hort Descriptive Interventional Case-control
Descriptive
Case-control
Prospective co-hort
Interventional
Descriptive studies?
Study cancer in populations having different diets, and compared them to countries (i.e. Chine and Canada), linking diet to cancer
Limitations to descriptive?
- Many variables in each country than just diet
- nutrient intake data difficult to collect in large groups
Case-control?
- Will use matched controls (people similar sex, age and social-economic status) to link and trends in developing cancer, asking about their long-term diet Hx
- Earlier diets reported by pts with cancer are compared with matched controls w/o cancer
Case-control limitations?
- May use proxy respondent
- Possible recall and selection bias
- Retrospective, memory reliant
Prospective co-hort?
Will follow huge co-hort foe long period of time, and periodically assessing diet and development of cancer
Limitations of prospective co-horts?
- Need thousands of people to be enrolled, as only small amount of people will develop cancer
- Difficult for rare types of CA
- Very costly
Interventional?
Two groups of randomized people on controlled, certain diets, will be followed over time to see who will develop cancer or not
Limitations of interventional?
- Adherence to dietary changes is difficult
- Blinding often not possible
- Optimal dosages need to be ascertained
- Duration is unknown, may be long
What kind of studies are the ONLY way that we can have a causal relationship? How?
- Interventional studies
- Primarily be done with markers of cancer, should not wait until cancer completely developed
How should epidemiological studies be viewed?
Complementary to metabolic, animal and in-vitro mechanistic studies
How does energy restriction reduce the development of cancer?
Since the rate of cell division is influenced by energy balance and growth rate.
In humans, growth rates and body size are indicators of _____
energy balance
What does adult height reflect?Adult weight?
Height reflects pre-adult nutrition, and weight reflects positive energy balance later in life
Is adult height associated with some kinds of cancers?
Maybe, but is NOT a cause - is more of an indication of pre-adult nutrition environment.
What may rapid growth rates before puberty be related to?
Future risk of breast and other cancers
What is adult obesity related to in terms of cancer?
Colon, kidney, pancreas, esophagus, endometrium, gall blader and liver
When does obesity increase risk of breast cancer?
Greater risk only AFTER menopause
Excess weight could account for ____ of cancers known to be influenced by nutrition
1/3
What are the main associations made between dietary fat and cancer?
Mostly to do with colon and breast cancer
What study in China determine about dietary fat intake?
NO association between dietary fat and cancer mortality
Do low fat diet reduce the development of cancer?
No - one study even showed higher risk
Is colon cancer relate to excess dietary fat?
No, more likely related to excess weight and low PA
What types of foods are associated with colorectal cancer?
ed meat and processed meats
Discuss the increased risk of processed meat and colorectal cancer
Increase of 49% probably risk in colorectal cancer with a 25-g increment increase of processed meat daily
Discuss the increases risk of red meat an colorectal cancer
Increase of 12-17% possible risk in colon cancer with 100 g increment increase in red meat daily
Is a 50% increase is risk that significant?
Depends on what the initial risk is, if we have a 1% initial risk, then it will only increase to 1.5%
The effect of ____ is very evident, while the level of evidence for ____ is probably (not as strong)
Processed meats
red meats
Explain the potential mechanisms of red and processed meats and the development of cancers
Nitrosamines are carcinogenic, where meats tend to contain a higher amount of nitrates and amino acids (protein).
-Nitrosamines formed in the stomach, and heme may encourage formation of these compounds
Besides the formation of nitrosamines, how does preparation of meats produce carcinogens?
High heat preparation (frying, broiling, grilling) may form polycyclic aromatic hydrocarbons and heterocyclic amines
(T/F) We can attribute increased risk of cancer and grilled meats
Fasle
Practical recommendation regarding meats and cancer?
- Choose leans, non-processed meats
- Replace with plant proteins
- Avoid burning meats, touching meat to flame
Diary products and cancer?
May decrease colon cancer, same effect may be observed in calcium supplements
Fruits and vegetables and cancer?
-Contain phytochemicals with potential anti-carcinogenic properties, associated with lower risk of CA
Recent studies are showing weaker links between F&V and overall cancer reduction rate, why?
-Limitations of categories of foods in FFQ (i.e. french fires and baked potatoes in same category)
Lycopene?
Decr prostate CA
Cruciferous veg?
Decrease several CA
Allium veg?
Stomach CA
Folate-rich F&V a?
Decr colon CA
Citrus F&V?
Decr lung CA
Proposed mechanisms between dietary fibres and reduced cancer risk?
Fibres may dilute or bind to carcinogens, limit the contact of the carcinogen with the mucose (increasing transit), alter colonic flora, reduce pH
How does dietary fibre alter colonic flora?
May serve as a substrate to produce SCFA, such as butyrate which has anti-proliferative effects against cancer
Recommendation on fibres?
Good level of evidence, increase intake of high-fibre foods
What is a VERY well-known cause of cancer?
Alcohol
Cancers and alcohol?
Upper GI –> oral cavity, larynk, esophagus, andliver
What increases risk of cancer when combined with high alcohol intake?
Cigarette smoking
Proposed mechanism of alcohol and cancer?
Direct contact of the alcohol within the mucosal lining of the GI tracts, an then toxicity int he liver
What may increase risk of breast and colon cancer?
> 2 drinks/day
Why is alcohol associate with increased risk of breast and colon cancer?
May be due to “anti-folate” effect of diet of alcohol, mimicking the effects of a diet low in methionine and folate
High intake of ___ reduces the risk of breast cancer associated with ____
folate
alcohol
Mechanism for calcium and cancer?
Calcium may (1) bind to the toxic, secondary bile acids and the ionized FA to form soaps within the lumen and (2) educe proliferation and inducing apoptosis.
Threshold of calcium to see beneficial effects?
700-800 mg/day
Recommendation for calcium and cancer?
Reach calcium RDA through foods, then supplement if needed
Population with greater sun exposure (Vit D) experience lower rates of what ?
Breast, colon and prostate cancers
25 (OH) D can cancer?
Circulating levels of 25(OH)D are generally inversely proportional to colorectal cancer
Vit,C, E and cancer?
Potential roles in reducing cancer risks through antioxidant species and ROS
Are antioxidants strongly recommended for prevention of cancer?
NO, and epi and intervention trials have no consistently supported a role in cancer risk
How does selenium act against oxidative stress?
Selenoproteins are incorporated into glutathione peroxidases
Low folate intake and cancer?
Higher risk of colorectal, breast, cervical
Are folate supplements recommended?
NO, although some studies suggest reduced risk of colorectal cancers, some increases recurrence of adenomas
Explain the controversy surrounding B-carotene supplementation and lung cancer?
We observed that increased lung Ca was associated with low Vit A intake, however 4 major trails of B-carotene supplementation resulted in null or adverse effects (in smokers, especially when combined with alcohol)
Bottom line on b-carotene supplements?
Increase risks of lung cancer, especially in smokers and increased alcohol intake
CONVINCING evidence surrounding decreasing cancer risk?
PA in colon cancer
CONVINCING evidence surrounding increasing cancer risk?
- Overweight/obese
- Alcohol
- Processed meet
- High dose b-carotene (lung)
- Alfatoxins (liver)
PROBABLE evidence surrounding decreased cancer risks?
- PA (breast)
- Calcium (colon)
- Whole grains, fibre (colon)
- Coffee (liver, uterus)
PROBABLE evidence surrounding increased cancer risk?
- Red meat (colorectal)
- Salt-preserved foods (stomach)
Limited/suggestive evidence surrounding decreased cancer risk?
- Carotenoids, vit C, veg
- Fish, vitD
Limited/suggestive evidence surrounding increased cancer risk?
- Grilled/BBQ meat (heterocyclic amines, polycyclic aromatics)
- Nitrosamines from hem
Limited / no conclusion surrounding increased cancer risk?
-Omega -3, carotenoids, B vitamins, folate, vit C, D,E, non-nutritive plants, garlic, soy, sugar, tea
What probable evidence decreases risk of premenopausal breast CA?
-Vigorous PA, body fatness, lactation
What probable evidence increases risk premenopausal breast CA?
Alcoholic drinks, greater BW
What is convincing evidence that increases risk of premenopausal breast CA?
Adult attained height
What probable evidence decreases risk of post-menopausal breast CA?
PA, body fatness in young adulthood, lactation
What convincing evidence increases risk of post-menopausal breast CA?
Alcoholic drinks, body fatness, adult weight gain, adult attained height
Discuss the risk of adult attained height and cancer
Is unlikely to influence the risk of cancer, however is a marker for genetic, hormonal, environmental and nutritional factors affecting growth
Convincing evidence deceasing risk of colorectalCA?
PA
Probably evidence deceasing risk of colorectal CA?
-Whole-grains, food containing dietary fibre, dairy products, calcium supplements
Limited/suggestive evidence deceasing risk of colorectalCA?
Vit C, Vit D, fish, multivitamin supplements
Convincing evidence increasing risk of colorectalCA?
- Processed meat
- Alcoholic rinks
- Body fatness
- Adult attained height
Probable evidence increasing risk of colorectalCA?
Red meat
Limited/suggestive evidence increasing risk of colorectalCA?
- Low intake of non-starchy veg, fruits
- Foods containing heme iron
Convincing evidence increasing lung cancer risk?
Arsenic in drinking water
High-dose beta-carotene
