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The Continuous Update Project | Prof. Martin Wiseman
The document outlines the Continuing Update Project by the World Cancer Research Fund, focusing on the relationship between nutrition, physical activity, and cancer risk. It presents evidence on dietary factors associated with cancer prevention and highlights the importance of avoiding tobacco and maintaining a healthy body weight. The findings also stress the need for further research to solidify links between diet and cancer outcomes, particularly for breast cancer survivors and prostate cancer patients.
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The Continuous Update Project | Prof. Martin Wiseman
- 1. The Continuous UpdateProject Breast cancer survivors and prostate cancer World Cancer Research Fund International, London UK Professor Martin Wiseman FRCP FRCPath FAfN NIHR BRC Southampton and University of Southampton
- 2. Who we areWhat we do AICR (1982) WCRF UK (1990) WCRF Netherlands (1994) WCRF Hong Kong (1997) WCRF International (1999) Fund research on the relationship of nutrition, physical activity and body weight to cancer risk Interpret the accumulated scientific literature to derive Recommendations for Cancer Prevention Educate people through our national Health Information programmes Advocate effective policies to help people and populations to reduce their chances of developing cancer
- 4. Breast Global variation incancer incidence Colorectum
- 5.
- 6. 0 5 10 15 20 25 30 1960 1965 1970- '71 1973 - '77 1979 - '82 1983 - '87 1988 - '92 1995 1997 Colon Breast Cancer Incidence in Japan* * Per 100,000, world population standard CancerIncidence
- 8. Hanahan & Weinberg(2011) Cell; Hanahan & Coussens (2012) Cancer Cell Hallmarks of cancer Two enabling characteristics for acquiring hallmarks
- 10. WCRF/AICR EXPERT REPORT Themost authoritative • New method • Systematic reviews • Review of evidence separate from judgement • Panel of international experts • Predetermined criteria for judgements – Epidemiology – Mechanisms • Flexibility • Continuous update of evidence
- 12. NUTRITION AND CANCERS •ADIPOSITY – BREAST (PM), COLORECTUM, ENDOMETRIUM, OESOPHAGUS, PANCREAS, GALLBLADDER, KIDNEY, OVARY, PROSTATE (ADVANCED) • PHYSICAL (IN)ACTIVITY – COLON, BREAST • MEAT – RED AND PROCESSED – COLORECTAL • ALCOHOL – MPL, BREAST, COLORECTUM, LIVER • PLANT FOODS (F&V, PULSES, WHOLEGRAINS) – MPL, OESOPHAGUS, STOMACH, COLORECTAL (DF), LUNG • BREASTFEEDING – BREAST (MOTHER), OBESITY (CHILD)
- 13. The Panel emphasisesthe importance of not smoking and of avoiding exposure to tobacco smoke
- 14. USA UK BRAZILCHINA Mouth, pharynx, larynx 63 67 63 44 Oesophagus 63 71 50 33 Lung 36 33 36 38 Stomach 47 45 41 33 Pancreas 19 15 11 8 Gallbladder 21 16 10 6 Liver 15 17 6 6 Colorectum 50 47 41 22 Breast 33 38 22 11 Ovary 5 4 3 1 Endometrium 59 44 37 21 Prostate (advanced) 11 10 5 4 Kidney 24 19 13 8 Total for these cancers 30 32 25 24 Total for all cancers 21 24 17 20 Estimates of cancer preventability by appropriate diet, nutrition, physical activity and body fatness
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- 16. IMPACT OF OFFSPRINGSIZE AND GROWTH ON CANCER RISK
- 17. Height and risk ofCVD and cancer CVD Cancer
- 18. Continuous Update Project:CUP Same process for systematically reviewing evidence for 2007 Report Researchers at Imperial College London – CUP database of epi research – Systematically review the evidence Expert Panel – Draw conclusions – Make recommendations
- 19. CUP database Research Team SecondExpert Report databases
- 20. Grading criteria Predefined requirementsfor Number and types of studies Quality of exposure and outcome assessment Heterogeneity within and between study types Exclusion of chance, bias or confounding Biological gradient Evidence of mechanisms Size of effect
- 21. Grading the evidence Decreases risk Increases risk Strong evidence Convincing Probable Limited evidence Limited- suggestive Limited – no conclusion Strong evidence Substantial effect on risk unlikely Basis for recommendations
- 22. Year Publication 2010 Breast 2011Colorectum 2012 Pancreas 2013-14 Endometrium, ovary, breast cancer survivors, prostate 2015 Liver, bladder, kidney, gallbladder 2015-16 Stomach, oesophagus, lung 2016-17 Mouth, pharynx, larynx, nasopharynx, breast, colorectum 2017 Review Recommendations for Cancer Prevention Publications timetable
- 23.
- 24. Prostate cancer –sub-types Non-advanced Advanced Fatal
- 25. Prostate cancer –advanced Advanced – AJCC 1992 stage 3-4 – Advanced – Advanced or metastatic – Metastatic – Whitmore/Jewett 3-4 – Fatal (prostate specific) – High stage or grade – Gleason 7 or more
- 33. Issues for prostatecancer Heterogeneity of disease Screen detected Advanced or aggressive Fatal Characterisation of exposure Lycopene Calcium/dairy
- 34.
- 35. Breast Cancer SurvivorsIncluded Pre-menopausal women Post-menopausal women Incident in-situ breast cancer Incident invasive breast cancer
- 36. Criteria for StudyInclusion Randomised controlled trials ≥ 50 women ≥ 6 months follow-up Only 2 identified (both low-fat diet trials) Prospective cohort (follow-up) studies Primary analysis, secondary analysis or ancillary analysis of randomised controlled trials, or follow-up studies in breast cancer survivors
- 37. Exposures Included Specificfoods Micro- and macro-nutrients Dietary patterns Alcohol Overweight, obesity, underweight, weight change, BMI Body composition Dietary supplements Physical activity
- 38. Timing of Exposures Pre-diagnosis Within 12 months following diagnosis Period of intensive primary therapy (surgery, radiation, chemotherapy) From 12 months after diagnosis Patients may be receiving targeted therapy during this period (e.g. hormonal therapy, HER2neu, bone metastases prevention) Data may extend 20 years or more
- 39. Outcomes Included Totalmortality Breast cancer specific mortality Second primary breast cancer
- 40. Outcomes Included Totalmortality Breast cancer specific mortality Second primary breast cancer Not: recurrence, QoL, lymphoedema etc
- 41. Literature search (New searchfor CUP) 19831 unique records identified in Pubmed and Embase until 30th June 2012 and 18 articles found in handsearch 897 full-text articles retrieved and assessed for inclusion 319 articles on survival and health events in women with breast cancer 18952 records excluded on the basis of title and abstract 578 articles excluded for not fulfilling the inclusion criteria 85 no original data 278 did not report on the associations of interest 30 abstract/commentary 9 meta-analyses 94 irrelevant study design 33 follow-up less than 6 months 49 study smaller than 50 women 213 articles have mortality or any second primary cancer as study endpoints 106 articles excluded on health events other than death or second primary cancer in women with breast cancer
- 45. Issues Relevant to SurvivorResearch Confounding effects of Treatment types, efficacies, adverse effects Stage of disease Comorbidities Type of cancer Methodological Determining cause of death Screening for second primary breast cancer Increasing length of survival
- 46. • Various associationsalso found for: – Physical activity – Foods containing fibre – Foods containing soy – Total fat – Saturated fatty acids • Evidence not judged strong enough to conclude causal effects
- 49. Need for studiesthat control for confounding by clinical variables Randomised controlled trials Cohort studies with accurate diagnostic & treatment variables Future Considerations
- 50. Summary Although therewere significant associations between some exposures and outcomes, incomplete adjustment for potential confounders restricted the ability to ascribe causality. CUP Panel concluded that evidence is limited.
- 51. CONCLUSIONS • Nutrition (diet,body composition and physical activity) is key determinant of global cancer patterns • Evidence from epidemiology and mechanistic data • CUP is refining knowledge of risk factors – Heterogeneity of prostate cancer – Body fatness and advanced prostate cancer – Lycopene? Calcium/dairy? – Body fatness and early life events are important for many cancers – Poor nutrition is an adverse diagnostic factor in breast cancer – better studies needed to determine causality
- 52.
- 54. Summary: Before diagnosis- BMI Totalmortality Breast cancer mortality Second primary breast cancer N deaths RR (95%CI) N deaths RR (95%CI) N events RR (95%CI) High vs. Low 8318 1.41 (1.29-1.54) 9854 1.34 (1.23-1.46) 701 1.43 (0.87-2.34) Underweight vs. normal weight 4944 1.10 (0.92-1.31) 4479 1.02 (0.85-1.21) - - Per 5 kg/m2 6261 1.17 (1.13-1.21) 6600 1.17 (1.11-1.24) 701 1.21 (1.04-1.40) Premenopause 644 1.25 (1.10-1.43) 1350 1.06 (0.85-1.32) - - Postmenopause 1103 1.16 (1.01-1.34) 2866 1.15 (1.05-1.25) - -
- 55. Summary: Around diagnosis- BMI Totalmortality Breast cancer mortality Second primary breast cancer N deaths RR (95%CI) N deaths RR (95%CI) N events RR (95%CI) High vs. Low BMI 16925 1.27 (1.16-1.38) 10063 1.36 (1.23-1.50) 3478 1.30 (1.14-1.48) Premenopause 4604 1.28 (1.16-1.42) 586 0.96 (0.45-2.06) - - Postmenopause 4614 1.13 (1.03-1.23) 1067 1.57 (1.31-1.89) - - Underweight vs. normal weight 2598 1.23 (0.93-1.63) 1455 1.52 (1.26-1.84) - - Per 5 kg/m2 5875 1.11 (1.06-1.17) 1918 1.18 (1.11-1.25) 3186 1.13 (1.06-1.21)
- 56. Summary: After diagnosis –BMI Total mortality Breast cancer mortality Second primary breast cancer N deaths RR (95%CI) N deaths RR (95%CI) N events RR (95%CI) High vs. Low 2289 1.21 (1.06-1.38) 2 studies Both risk, 1 significant No studies Underweight vs. normal weight 1361 1.29 (1.02-1.63) Per 5 kg/m2 1703 1.08 (1.01-1.15) 4, 0%, p=0.52
- 57. Summary: physical activity Totalmortality Breast cancer mortality Events RR (95%CI) N, I2, P het Events RR (95%CI) N, I2, P het Before diagnosis Total H vs. L 505 0.83 (0.62-1.12) 2, 23%, p=0.25 338 0.80 (0.59-1.10) 2, 0%, p=0.88 Before diagnosis Recreational H vs. L 2892 0.74 (0.67-0.83) 8, 5%, p=0.39 1750 0.76 (0.61-0.95) 7, 49%, p=0.06 After diagnosis Total H vs. L 514 0.63 (0.41-0.97) 3, 44%, p=0.16 217 0.81 (0.48-1.36) 2, 0%, p=0.63 Per 10 MET- h/week 514 0.90 (0.79-1.03) 3, 79%, p=0.009 - - After diagnosis Recreational H vs. L 2337 0.61 (0.50-0.74) 5, 46% ,p=12 392 0.71 (0.45-1.12) 2, 33%, p=0.22 After diagnosis Recreational Per 10 MET- h/week 2337 0.81 (0.73-0.90) 5, 64%, p=0.03 - -
- 58. Summary: dietary fibre Totalmortality Breast cancer mortality Events RR (95%CI) N, I2, P het Events RR (95%CI) N, I2, P het Before diagnosis H vs. L 417 0.50 (0.35-0.73) 2, 0%, p=0.83 2 studies Non-sig risk Per 10g/d 443 0.68 (0.55-0.84) 3, 0%, p=0.41 After diagnosis H vs. L 1092 0.76 (0.58-0.98) 3, 0%, p=0.99 332 0.82 (0.57-1.20) 3, 0%, p=0.95 Per 10g/d 1092 0.88 (0.78-0.99) 3, 0%, p=0.97 332 0.93 (0.80-1.07) 3, 0%, p=0.64
- 59. Summary: isoflavones Total mortality Events RR(95%CI) N, I2, P het Before diagnosis H vs. L 624 0.87 (0.65-1.17) 3, 59%, p=0.06 After diagnosis H vs. L 794 0.70 (0.56-0.88) 3, 8%, p=0.33 Per 10mg/d 794 0.91 (0.83-1.00) 3, 68%, p=0.05
- 60. Summary: total fat Totalmortality Breast cancer mortality Events RR (95%CI) N, I2, P het Events RR (95%CI) N, I2, P het Before diagnosis H vs. L (g/d) 655 1.87 (0.76-4.57) 3, 90%, p<0.001 521 1.13 (0.71-1.77) 4, 54%, p=0.09 Per 10g/d 178 1.19 (1.01-1.41) 4, 82%, p=0.001 - - Per 10% energy 178 1.82 (1.41-2.36) 3, 0%, p=0.38 - - After diagnosis H vs. L (g/d) 1436 1.08 (0.90-1.30) 3, 24%, p=0.27 648 1.19 (0.94-1.50) 4, 0%, p=0.41 Per 10g/d - - 575 1.01 (0.95-1.08) 3, 24%, p=0.27
- 61. After diagnosis: saturatedfat Outcome Author Year Study design Number of events Contrast RR (95% CI) Total mortality Beasley 2011 Follow-up of cases from case- control study 525 13% vs. 7% energy 1.40 (1.06-1.87) Total mortality Holmes 1999 Cancer survivors of a cohort study (NHS) 378 Q5 vs. Q1 g/d 1.23 (0.89-1.69) Breast cancer mortality Beasley 2011 Follow-up of cases from case- control study 137 13% vs. 7% energy 1.55 (0.88-2.75) Breast cancer mortality Rohan 1993 Follow up of cases from case- control study 112 ≥45 vs <20g/d 1.65 (0.73-3.75) For each of total mortality and breast cancer mortality there were only two studies
- 62. Summary: Alcohol Total mortality Breastcancer mortality Second primary/ contralateral breast cancer N deaths RR (95%CI) N deaths RR (95%CI) N events RR (95%CI) Before diagnosis: High vs. Low 2650 0.93 (0.82-1.06) 1329 1.18 (0.81-1.72) - - Before : Per 1 drink/week 2676 1.00 (0.99-1.00) 1296 1.00 (0.97-1.02) - - After diagnosis: High vs. Low 3827 0.89 (0.72-1.09) 403 1.22 (0.88-1.69) 2347 1.19 (0.96-1.47) After diagnosis: Per 10g/d 3779 0.98 (0.93-1.03) 403 1.06 (0.79-1.42) 2347 1.01 (0.99-1.03)