NUTRITION AND CANCER
MDSC3103 HUMAN NUTRITION
Tropical Medicine Research Institute
Dr Kwesi Marshall
MAJOR LEARNING OBJECTIVES
To outline the major stages of carcinogenesis
To classify the major classes of cancer
To describe the major hallmarks of cancer
To list the principal causes of cancer
To highlight potential cancer-modulating
nutrients
To provide recommendations for reducing
cancer risk
LECTURE OUTLINE
Cellular processes
Cancer
Carcinogenesis
Causes of cancer
Diet, nutrition, and cancer
Panel recommendations
Summary
CELLULAR PROCESSES
‘NORMAL’ CELLULAR PROCESSES
Cell signalling
- Autocrine
- Paracrine
- Endocrine
Cell growth
Cell division/proliferation
Cell differentiation
Cell death
CANCER
WHAT IS CANCER?
A disease characterized by the loss of the
normal control of cell division, which typically
results in the inappropriate excessive
multiplication of cells.
CANCER CLASSIFICATION SCHEMES
Cancers are commonly characterized on the
basis of:
Tissue/cell types from which they develop
Cancer sites within the body
CANCER CELL CLASSIFICATION
Adenomas
Carcinomas
Gliomas
Leukaemias
Lymphomas
Melanomas
Sarcomas
CANCER SITE CLASSIFICATION
Bladder cancer
Breast cancer
Cervical cancer
Colorectal cancer
Kidney cancer
Mouth cancer
Liver cancer
Lung cancer
Oesophageal cancer
CANCER SITES
Ovarian cancer
Pancreatic cancer
Prostate cancer
Stomach cancer
Throat cancer
Uterine cancer
CARCINOGENESIS
STAGES OF CARCINOGENESIS
Initiation
- DNA damage and mutations in a single cell
Abnormal cell division
Promotion
Tumour (neoplasm) development
Cancer!
FACTORS THAT INFLUENCE
CARCINOGENESIS
Factors that are necessary for triggering cancer
development are referred to as initiators.
Factors that facilitate cancer development once
it has been initiated are referred to as
promoters.
In addition, factors that might protect against
the development of cancer are referred to as
anti-promoters.
FIG 1. SCHEMATIC REPRESENTATION
OF A HYPOTHETICAL CANCER
PROMOTING PROCESS
CANCER HALLMARKS
There are six ‘hallmarks’ of cancer.
CANCER HALLMARK 1
Unlimited cell replication
CANCER HALLMARK 2
Insensitivity to growth inhibitory signals
CANCER HALLMARK 3
Evasion of apoptosis
CANCER HALLMARK 4
Sustained angiogenesis
CANCER HALLMARK 5
Invasion and metastasis
CANCER HALLMARK 6
Growth signal autonomy
FIG. 2. PUTTING IT ALL TOGETHER:
THE SIX HALLMARKS OF CANCER
CAUSES OF CANCER
MAJOR CLASSES OF CANCER CAUSES
Broadly divided into:
Endogenous causes
Exogenous causes
Chance!
ENDOGENOUS CAUSES OF CANCER
Inherited mutations
- Tumour suppressor gene mutations
- Oncogenes (Ras, ERBB2)
Somatic gene mutations
Epigenetic modulation
ENDOGENOUS CAUSES OF CANCER
Oxidative stress
Inflammation
Hormones
- Oestrogen
- Insulin-like growth factor
- Leptin
EXOGENOUS CAUSES
Chemicals
Infectious agents
- Viruses
- Bacteria
Radiation
Nutritional carcinogens
CHEMICAL CARCINOGENS
Natural toxicants
- Aflatoxin B (Aspergillus sp. - Mould)
Synthetic agents
- Tobacco smoke
- Polycyclic aromatic hydrocarbons
- Heterocyclic amines
- Diethylstilboesterol (DES)
VIRAL CAUSES OF CANCER
Human papilloma virus
Epstein-Barr virus
Hepatitis B
Hepatitis C
BACTERIAL CAUSES OF CANCER
Helicobacter pylori
RADIATION
Ionising radiation
- Cosmic radiation
- Natural radioactivity
- Medical exposure
- Nuclear accidents
UV radiation
- UVA
- UVB
DIET, NUTRITION, AND CANCER
FIG. 3. FOOD, NUTRITION, OBESITY,
PHYSICAL ACTIVITY, AND CELLULAR
PROCESSES LINKED TO CANCER
CANCER: A SUMMARY
Multifactorial process
Multiple hits
Long latent period
Components of food might
- directly cause cancer
- directly protect against cancer
- Indirectly influence the process
NUTRITION AND CANCER:
A MAJOR QUESTION
HOW MIGHT LIFETIME NUTRITIONAL
EXPOSURES INFLUENCE CANCER
DEVELOPMENT?
A HIERARCHY OF EVIDENCE
Meta-analyses of randomized controlled trials
(RCTs)
RCTs
Non-randomized trials
Observational
- cohort
- case-control
- ecological
PUTATIVE DIETARY PRO-
CARCINOGENS
n-6 PUFAs (Omega 6)
Saturated fatty acids
Trans fatty acids
Dietary mutagens
- Aflatoxin B (positively associated with liver
cancer)
Alcohol
PUTATIVE DIETARY ANTI-
CARCINOGENS
Carotenoids (lycopene, lutein)
Retinoids
Vitamin C
Vitamin E
Phytoestrogens
Phytosterols
Organosulphur compounds
Isothiocyanates
MORE PUTATIVE DIETARY ANTI-
CARCINOGENS
Selenium
Zinc
n-3 PUFAs (Omega 3)
Folate
Dietary restriction
Dietary fibre
PROBLEMS INTERPRETING POSSIBLE
DIET-CANCER ASSOCIATIONS
Diversity of potentially important and often
correlated dietary factors
Relatively small influence (effect size) on risk
Dietary intake estimates are typically inaccurate
PANEL RECOMMENDATIONS
PANEL RECOMMENDATIONS
The World Cancer Research Fund’s
recommendations can be divided into:
General recommendations
Special recommendations
Format of recommendations
- Public health goals
- Personal recommendations
RECOMMENDATION 1
BODY FATNESS
Be as lean as possible within the normal range
of body weight
RECOMMENDATION 2
PHYSICAL ACTIVITY
Be physically active as part of everyday life
RECOMMENDATION 3
FOODS AND DRINKS THAT PROMOTE WEIGHT
GAIN
Limit consumption of energy-dense foods
Avoid sugary drinks
RECOMMENDATION 4
PLANT FOODS
Eat mostly foods of plant origin
RECOMMENDATION 5
ANIMAL FOODS
Limit intake of red meat and avoid processed
meat
RECOMMENDATION 6
ALCOHOLIC DRINKS
Limit alcoholic drinks
RECOMMENDATION 7
PRESERVATION, PROCESSING,
PREPARATION
Limit consumption of salt
Avoid mouldy cereals (grains) or pulses
(legumes)
RECOMMENDATION 8
DIETARY SUPPLEMENTS
Aim to meet nutritional needs through diet alone
SPECIAL RECOMMENDATION 1
BREASTFEEDING
Mothers to breastfeed; children to be breastfed
SPECIAL RECOMMENDATION 2
CANCER SURVIVORS
Follow the recommendations for cancer
prevention
SUMMARY
SUMMARY POINTS
Cancers generally develop from mutations in a
few genes of a single cell.
Gene mutations that lead to cancer depend on
endogenous processes, exogenous mutagens
and chance.
Obesity and alcohol consumption have been
associated with particular cancers.
Dietary-derived nutrients might play important
roles in protecting against certain cancers.