9. Nutrition and cancer prevention

Advantages of in vitro studies in cancer research

• Underlying mechanisms

• short duration

• inexpensive

• controlled conditions

• toxic concentrations

Disadvantages of in vitro studies in cancer research

• not normal cells

• limited number of compounds

• metabolism lacking

Advantages of animal studies in cancer research

• Underlying mechanisms

• Tumor development

• Controlled conditions

• Toxic concentrations

Disadvantages of animal studies in cancer research

• Metabolism differs

• Not part of rodent diet

• No human dietary pattern

Problem in all observational studies

• Causality: Causality is the relationship between an event (the cause) and a second event (the effect) where the first event is responsible for producing the second

  • Sometimes links will be made that are not related (correlation is not causation)

• Reverse causation: a logical error where you assume that variable X causes variable Y, when the true causal relationship actually runs in reverse, with Y causing X

• Confounding: the observed association between an exposure and outcome is caused by a third factor that is not part of the biological pathway

Two types of observational studies?

• Cohort: ask if exposed or not and compare incidence

• Case-control: ask diseased/non-diseased their prior exposure

Design of a case-control study

Problem in case-control studies

• Recall bias

• Not being able to recall correctly or lying

• Selection bias, not representative cases & controls

• Non-response depending on exposure (if you are smoking you might be less likely to participate)

• Reverse causality: chicken or egg

Design of a prospective cohort study

How is relative risk calculated?

Limitations of cohort studies

• Large studies, depending on occurrence of disease

• Long follow-up, depending on time to cancer diagnosis, possible loss of participants (selection bias)

• Misclassification of intake (information bias)

• Within cohort range of intake may be limited: may be hard to detect risks with very high or very low intake levels.

• Diets are not constant over time, repeated measurements

Advantages of observational studies

• Real life situation

• Long duration

• Disease endpoints

• Specific compounds, foods and diets

• Also unhealthy

Design of a randomized controlled trial (intervention study)

Advantages of RCTs

• Controlled conditions

• Confounding minimalized

• Cause-effect

• Specific compounds, foods and diets

Disadvantages of RCTs

• Only ‘healthy’ foods due to ethics

• Labor intensive, expensive

• Intermediate endpoints

• Lack of compliance

• Short duration

• Timing of exposure

• Double blinded

The evidence pyramid

How to understand forest plot in Meta-Analysis

Heterogeneity

the results or methods of the different studies vary significantly more than what you would expect by pure random chance alone

• To explain heterogeneity you can attempt to organize studies by country or by types of breast cancer

When is evidence convincing

• Strong and unlikely to change in future

• no unexplained heterogeneity

• At least 2 independent cohort studies

• Good quality studies that account for error

• Dose response

• Robust evidence from laboratory studies

When is evidence probable?

• No unexplained heterogeneity

• At least 2 independent cohort or 5 case-control studies

• Good quality studies that account for error

• Dose response

• Plausible evidence from laboratory studies

What is the largest risk factor for most types cancer?

Overweight, especially the fat surrounding the organs

For which cancer is diet the most important in decreasing the risk?

For colorectal cancer, large bowel is exposed to everything we eat.

What are the possible mechanisms behind body fatness and cancer?

• Metabolic Syndrome and Insulin Resistance: Higher body fatness increases insulin resistance and elevates circulating growth factors, such as insulin-like growth factors, which can promote abnormal cell growth

• Chronic Inflammation: Fat accumulation surrounding internal organs induces systemic chronic inflammation, altering key inflammatory cytokines such as TNF, IL-6, and MIF

• Adipokine Imbalance: Excess adiposity alters adipokine signaling, specifically leading to an increase in leptin and a decrease in adiponectin levels

• Hormonal Changes: Adipose tissue influences hormone production, resulting in increased levels of sex hormones (such as estrogens) as well as growth hormones, which can stimulate cell proliferation in hormone-sensitive tissues

• Vitamin D Deficiency: Body fatness is also associated with lower available levels of vitamin D, which is noted as an additional potential mechanism

Effect of increase in physical activity

• Reduces the risk of:

  • Colon cancer

  • Breast cancer

  • Endometrium cancer

Consumption of ‘fast foods’ and other processed foods

• = high in fat, starches or sugars

• Should be limited

• To control calorie intake and maintain a healthy weight.

Ultraprocessed foods

• Hard to define, not based on calories but on processing

• Ultra-processed foods: foods that contain ingredients you wouldn’t normally use at home, with additives like preservatives, sweeteners and artificial colors and stabilizers. Often with long shelf life, e.g. ice cream, sausages, crisps, fizzy drinks and instant soups

• However, there are also ultraprocessed foods that are good for you like vegetarian burgers. Therefore not all ultraprocessed food causes cancer.

Is microwaving carcinogenic?

• No

• However, often foods (like ready to eat meal) that you microwave are high in sugar, fat, salt, etc.

• Which IS carcinogenic

What cancer risks are reduced by the consumption of fruits and vegetables?

• Mouth

• Pharynx

• Larynx

• Lung (fruits)

The reason why is not clear.

Effect of dietary fibre on… cancer

Decreases the risk of colorectal - strong evidence!

Mechanism of dietary fibre and colorectal cancer

1. Dietary fibre protects against colorectal cancer through several proposed biological mechanisms^[1][2]:

2. Formation of Short-Chain Fatty Acids (SCFAs): Gut bacteria ferment dietary fibre in the colon to produce short-chain fatty acids, such as butyrate. Butyrate helps reduce cell proliferation and induces apoptosis (programmed cell death) in damaged or abnormal cells.

3. Reduction of Intestinal Transit Time: Dietary fibre speeds up transit time through the colon, which minimizes the contact time between carcinogenic substances in the intestinal contents and the colonic mucosa

4. Reduction of Insulin Resistance: Fibre intake is suggested to help lower insulin resistance, which is linked to a reduced risk of cancer development.

5. Source of Phytoestrogens: Fibre-rich plant foods serve as important sources of protective bioactive compounds, including phytoestrogens.

Can eating be replaced with supplements?

• In a study with 30000 heavy smokers, the half who was given beta carotene supplements had a higher risk of cancer

• Shows that there is a safe intake, not too much not too little.

• Therefore it is important to consider dosage, combination of compounds and timing.

• Therefore, do not use supplements for cancer prevention!

Consumers vs nutritions on what increases the risk of cancer

In the future

There should be guidelines on dairy products, coffee, ultra-processed foods, vegetarian diets

Future research

• Low/middle income countries really need to be researched as the incidences of breast, prostate and colorectum cancer is increasing in Africa