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.