the continuous update project | prof. martin wiseman
TRANSCRIPT
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The Continuous Update ProjectBreast 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
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Who we are What 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
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Breast
Global variation in cancer incidence
Colorectum
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Migration data
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Cancer Incidence in Japan*
* Per 100,000, world population standard
Ca
nce
r In
cid
en
ce
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Hanahan & Weinberg (2011) Cell; Hanahan & Coussens (2012) Cancer Cell
Hallmarks of cancer
Two enabling characteristics for acquiring hallmarks
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WCRF/AICR EXPERT REPORT The most 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
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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)
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The Panel emphasises the importance of not smoking and of avoiding exposure to tobacco smoke
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USA UK BRAZIL CHINA
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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CANCER FREQUENCY AND AGE
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IMPACT OF OFFSPRING SIZE AND GROWTH ON CANCER RISK
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Height and risk of CVD and cancer
CVD Cancer
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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
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CUP database
Research Team
Second Expert Report databases
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Grading criteria
Predefined requirements for
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
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Grading the evidenceDecreases risk
Increases risk
Strong evidence
Convincing
Probable
Limited evidence
Limited - suggestive
Limited – no conclusion
Strong evidence
Substantial effect on risk unlikely
Basis for recommendations
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Year Publication
2010 Breast
2011 Colorectum
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
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Prostate cancer
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Prostate cancer – sub-types
Non-advanced
Advanced
Fatal
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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
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Issues for prostate cancer
Heterogeneity of diseaseScreen detectedAdvanced or aggressiveFatal
Characterisation of exposureLycopeneCalcium/dairy
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Breast Cancer Survivors
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Breast Cancer Survivors Included
Pre-menopausal women Post-menopausal women Incident in-situ breast cancer Incident invasive breast cancer
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Criteria for Study Inclusion
Randomised controlled trials≥ 50 women≥ 6 months follow-upOnly 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
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Exposures Included Specific foods Micro- and macro-nutrients Dietary patterns Alcohol Overweight, obesity, underweight, weight
change, BMI Body composition Dietary supplements Physical activity
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Timing of ExposuresPre-diagnosis Within 12 months following diagnosis
Period of intensive primary therapy (surgery, radiation, chemotherapy)
From 12 months after diagnosisPatients may be receiving targeted therapy
during this period (e.g. hormonal therapy, HER2neu, bone metastases prevention)
Data may extend 20 years or more
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Outcomes Included
Total mortality
Breast cancer specific mortality
Second primary breast cancer
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Outcomes Included
Total mortality
Breast cancer specific mortality
Second primary breast cancer
Not: recurrence, QoL, lymphoedema etc
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Literature search(New search for 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 data278 did not report on the associations of interest30 abstract/commentary9 meta-analyses94 irrelevant study design33 follow-up less than 6 months49 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
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Issues Relevant to Survivor Research
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
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• Various associations also found for:– Physical activity– Foods containing fibre– Foods containing soy– Total fat– Saturated fatty acids
• Evidence not judged strong enough to conclude causal effects
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Need for studies that control for confounding by clinical variables
Randomised controlled trialsCohort studies with accurate diagnostic &
treatment variables
Future Considerations
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Summary
Although there were 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.
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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
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Thank you!
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Summary: Before diagnosis- BMI
Total mortality Breast cancer mortalitySecond 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) - -
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Summary: Around diagnosis- BMI
Total mortality Breast cancer mortalitySecond 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)
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Summary: After diagnosis – BMI
Total mortality Breast cancer mortalitySecond 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
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Summary: physical activity Total mortality
Breast cancer mortality
EventsRR (95%CI)N, I2, P het
EventsRR (95%CI)N, I2, P het
Before diagnosisTotal
H vs. L 5050.83 (0.62-1.12)2, 23%, p=0.25
3380.80 (0.59-1.10)2, 0%, p=0.88
Before diagnosis Recreational
H vs. L 28920.74 (0.67-0.83)8, 5%, p=0.39
17500.76 (0.61-0.95)7, 49%, p=0.06
After diagnosisTotal H vs. L 514
0.63 (0.41-0.97)3, 44%, p=0.16
2170.81 (0.48-1.36)2, 0%, p=0.63
Per 10 MET-h/week
5140.90 (0.79-1.03)3, 79%, p=0.009
- -
After diagnosisRecreational
H vs. L 23370.61 (0.50-0.74)5, 46% ,p=12
3920.71 (0.45-1.12)2, 33%, p=0.22
After diagnosisRecreational
Per 10 MET-h/week
23370.81 (0.73-0.90)5, 64%, p=0.03
- -
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Summary: dietary fibre
Total mortalityBreast cancer mortality
EventsRR (95%CI)N, I2, P het
EventsRR (95%CI)N, I2, P het
Before diagnosis H vs. L 4170.50 (0.35-0.73)2, 0%, p=0.83
2 studiesNon-sig risk
Per 10g/d 4430.68 (0.55-0.84)3, 0%, p=0.41
After diagnosis H vs. L 10920.76 (0.58-0.98)3, 0%, p=0.99
3320.82 (0.57-1.20)3, 0%, p=0.95
Per 10g/d 10920.88 (0.78-0.99)3, 0%, p=0.97
3320.93 (0.80-1.07)3, 0%, p=0.64
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Summary: isoflavones
Total mortality
EventsRR (95%CI)N, I2, P het
Before diagnosis H vs. L 6240.87 (0.65-1.17)3, 59%, p=0.06
After diagnosis H vs. L 7940.70 (0.56-0.88)3, 8%, p=0.33
Per 10mg/d 7940.91 (0.83-1.00)3, 68%, p=0.05
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Summary: total fat
Total mortalityBreast cancer mortality
EventsRR (95%CI)N, I2, P het
EventsRR (95%CI)N, I2, P het
Before diagnosis H vs. L (g/d) 6551.87 (0.76-4.57)3, 90%, p<0.001
5211.13 (0.71-1.77)4, 54%, p=0.09
Per 10g/d 1781.19 (1.01-1.41)4, 82%, p=0.001
- -
Per 10% energy 1781.82 (1.41-2.36)3, 0%, p=0.38
- -
After diagnosis H vs. L (g/d) 14361.08 (0.90-1.30)3, 24%, p=0.27
6481.19 (0.94-1.50)4, 0%, p=0.41
Per 10g/d - - 5751.01 (0.95-1.08)3, 24%, p=0.27
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After diagnosis: saturated fat
Outcome AuthorYear
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. Q1g/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
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Summary: Alcohol
Total mortalityBreast cancer 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
26761.00 (0.99-1.00)
12961.00 (0.97-1.02) - -
After diagnosis:High vs. Low
38270.89 (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)