Foods which protect against cancer David Topping CSIRO Health Sciences and Nutrition Adelaide SA

1. Foods which protect against cancerDavid Topping CSIRO Health Sciences and NutritionAdelaide SA

2. Are Cancers Important? Collectively cancers are the major source of premature death in Australia, they are also major causes of morbidity. Important cancers include: • Breast (women) • Trachea, bronchus and lung • Colon and rectum • Urinogenital (men and women) • Circulatory (leukaemias, lymphomas) • Skin Numerical or economic importance does necessarily relate to perceived importance eg skin (which is visible) is seen as more important than colon (which is not).

3. Cancers as Age-standardised Causes of Death in Australia in 1999

4. Do Diet and Lifestyle Relate to Cancer Risk? • Unquestionably - yes. The best example is cigarette (not necessarily tobacco) use and lung cancer - found rarely in non-cigarette smokers. • The genetic component in cancer is relatively small. For example, 3-4% of risk of colon cancer is genetic and >80% is diet-related. • One of the problems with assessing the relationship is that there are few markers for cancer apart from the disease itself. This contrasts with vascular disease where there are indices such as plasma lipids, cholesterol etc. • The micronucleus is one index but it indicates genetic damage rather than cancer risk.

5. S phase OH* anaphase

6. Means of Gathering Evidence that Diet and Lifestyle Relate to Cancer Risk There are several routes. All have strengths and weaknesses and and together they point to a strong role for the effectiveness of behavioral modification in lowering risk. • Epidemiology - comparison of populations (drawback - only shows association, not causation and there are methodological issues) • Human interventions - feeding or other trials (drawbacks - can only diminish risk, relatively few biomarkers, may not distinguish between disease causation and progression) • Animal models - chemically or genetically induced cancer (drawback - relevance to humans) • Cell and other systems - cancer cells incubated with putative protective agents (drawback - relevance to the in vivo situation).

7. Some Likely Contributors to Avoidable Cancers

8. Diet and Cancer Risk • If diet is linked to cancer risk, then it is important to know which components protect and which increase risk. • As many of the data are derived from population studies, confounding factors need to be eliminated. • Alcohol consumption and gastric cancer is a classic case.

9. Alcohol, Smoking and Gastric Cancer - A Case Study in Confusion • Gastritis and reflux are established risk factors for gastric cancer. Cigarette smoking (through “stress”) and alcohol consumption were considered to be risk promoters. • However, infection with a bacterium (H pylori) is now regarded as a primary carcinogenic risk and its control is a primary preventive strategy. • Heavy drinkers are likely to be heavy smokers and cigarette use increases cancer risk and lowers immune status. • Alcoholic beverages (especially beer and wine) are strongly bactericidal against H pylori and population studies controlling for smoking show protection with moderate consumption.

10. Some Possible Protective Food Components

11. Potential Health Benefits of n-3 Fatty Acids N-3 Fatty acids have great potential to improve health in several areas: • CHD - lowering of plasma triglycerides, lower blood clotting, lowered risk of arrhythmias (sudden heart attack). • Cancer - induction of apoptosis (ie cancer cells are induced to die), changes in fat metabolites (eicosanoids). • Inflammatory conditions - lowered cytokine and eicosanoid production. • Foetal and infant development (including brain function). • Improved central nervous function (including depression and other mental conditions).

12. N-3 Fatty Acids and Colon Cancer Risk Colon cancer is a major health problem. Several lines of evidence suggest that n-3 fatty acids (eicosapentaenoic - EPA- and docosahexaenoic - DHA - acids) may be highly protective. Australian n-3 intakes are low. • Certain populations (eg the Japanese, South African fishermen) eat little fibre but have high n-3 intakes and low rates of colon cancer. • Animal studies indicate protection by n-3 fatty acids against experimentally-induced colon cancer. • At-risk groups (eg persons with Crohn’s disease) show remission with n-3 supplements. • EPA induces apoptosis in isolated cancer cells.

13. Clinical Results during Treatment with Enteric -coated Fish Oil or Placebo in Patients with Crohn’s Disease in Remission

14. Induction of Apoptosis by 50 M EPA in HT 29 Colorectal Tumor Cells (Fyfe, 1996)

15. Fibre, Starch and Colon Cancer • Australia has done well in increasing fibre intakes at the population level but cancer rates remain high. • Importantly, epidemiology and human interventions suggest that protection by fibre is relatively weak and starch may be more protective. • Why should this occur? Probably because they are complementary - fibre is a bulking agent and starch (as resistant starch) is fermented more. • However, methodological problems may contribute. • Australian starch consumption is very low – we are working to increase it.

16. Starch Intake and Male Large Bowel Cancer Incidence

17. Escape of food components from the small intestine into the large intestine Food fibre, starch, protein, fat, sugars (lactose etc) Small intestine Large intestine • Undigested starch = resistant starch (RS)

18. What are Short Chain Fatty Acids? • Short chain fatty acids (SCFA) are small (1-6 carbon) organic acids. • They are important because, in humans, they effect many of the benefits of fibre and resistant starch in the large bowel. • There are three major SCFA but one acid, butyrate, is especially important as it is thought to promote large bowel health and protect against colo-rectal cancer. • RS fermentation appears to favour butyrate production.

19. The main SCFA are acetate, propionate and butyrate. Carbohydrates are the principal substrates. Cx(H2O)y + N + Bacteria SCFA + CO2 + H2+ CH4 + More Bacteria + H2O Essentials of colonic SCFA production

20. So, which foods (and what else) ? Eat a variety of foods (including starchy foods). Lower intakes of total and saturated fats. Ensure a good intake of n-3 fatty acids. Pick your parents carefully, try not to get old and be male (breast and female genital cancer), female (prostate cancer). Don’t smoke cigarettes, Stay out of the sun.