1. Chapter 8 Cancer

2. Chapter overview Introduction Carcinogenesis Physical activity and colorectal cancer Physical activity and breast cancer Physical activity and other cancers Mechanisms Population-attributable risk Physical activity in cancer survivors Summary

3. Definition and risk Cancer is not one disease, but a set of diseases characterized by unregulated cell growth leading to invasion of surrounding tissues and spread to other parts of the body. In developed countries, the lifetime risk of developing cancer is around 1 in 3.

4. Role of environmental factors in cancer causation: migrant studies

5. Normal cells Reproduce themselves exactly; stop reproducing at the right time; stick together in the right place (cell adhesion); self-destruct if they are damaged (apoptosis); become specialized or mature.

6. Cancer cells Carry on reproducing; do not obey signals from neighbouring cells; can become detached from the primary tumour and travel to other parts of the body; do not become specialized, but stay immature; do not die if they move to another part of the body.

7. Carcinogenesis Damage to a cell’s DNA is called mutation. Cancer derives from an accumulation of errors. Few cancers are familial. Most cancers are initiated by exposure to some environmental agent – chemicals, radiation, viruses. There is no single cause – cancer is a multifactorial disease.

8. Risk factors Age – the most important factor; genes that increase susceptibility, e.g. two genes are known to increase risk for breast cancer; impaired immune function, e.g. in AIDs; diets high in fat, meat, salt or alcohol increase risk for some cancers; agents in the environment, e.g. tobacco smoke, sun, radiation, workplace hazards, asbestos; viruses can cause genetic changes in cells that make them more likely to become cancerous, e.g. hepatitis B increases risk for liver cancer.

9. US Nurses’ Health Study: colon cancer risk

10. Colon cancer risk in people with high energy intake and high BMI Activity statusOdds ratio95% CI Low physical activity3.352.09–5.35 High physical activity1.280.81–2.03

11. Evidence for the relation between physical activity and colon cancer Consistent across: –occupational and leisure activity –different study designs; comparing most active with least active, median relative risk is 0.7; independent of confounding factors; some evidence of dose–response; overall, evidence classed as ‘convincing’.

12. Canadian case-control study: breast cancer risk

13. Breast cancer risk in Nurses’ Health Study: dose–response evident

14. Evidence for the relation between physical activity and breast cancer Around 60 observational studies; consistent when total activity was measured; independent of confounding factors; comparing most active with least active, median relative risk is 0.8 (20% risk reduction); overall, evidence ‘convincing’, but interaction with menopausal status still to be clarified.

15. Potential mechanisms Systemic: –low levels of metabolic hormones, e.g. insulin, IGFs; –improved weight regulation, low body fatness; –enhanced immune function in moderately active people. Site-specific –sex steroid hormones, e.g. oestrogen and breast cancer risk; –for colon cancer, bowel transit time.

16. Changes in bowel transit time with six weeks of running training

17. Preventive potential Population-attributable risk estimates from International Agency for Research on Cancer (2002): 13–14% for colon cancer 11% for postmenopausal breast cancer

18. Evidence linking physical activity with cancer risk Cancer sitePlausibilityEvidence level ColonSeveral hypothesesConvincing BreastSeveral hypotheses Postmenopausal – convincing/probable: premenopausal – limited EndometriumA few hypothesesProbable ProstateSome hypothesesPossible PancreasAt least two hypotheses Possible, limited evidence LungNone known Possible, limited evidence

19. Summary I Cancer is major source of morbidity and mortality. Risk factors vary by tumour site. Carcinogenesis disrupts the orderly fashion in which normal body cells grow, divide and die. Physical activity is associated with reductions in the risk of several site-specific cancers. Evidence is strongest for cancers of the colon and breast.

20. Summary II Dose–response relationships are not well described. At least 30–60 minutes per day of moderate-to- vigorous activity may be needed for optimal reduction in risk of colon and breast cancer. Potential mechanisms can be advanced, some systemic, some site-specific.