Continuous Update Project: Database update and systematic literature review. Presentation given by Teresa Norat, Principal Investigator Continuous Update Project, Imperial College London.

1. Continuous Update Project:
Database update and systematic
literature review
Teresa Norat
Principal Investigator Continuous Update Project, Imperial College London

2. Protocol
Research topic :
 The associations between food, nutrition and physical activity and
 Cancer risk
 Mortality and second cancers in breast cancer survivors.
Main objective :
 Summarize the evidence from prospective studies and randomised
controlled trials (case-control studies if requested by the Panel).
Search strategy:
 Medline, Central, ClinialTrials.gov
 Hand search of references (reviews, meta-analysis, recent relevant
papers)

3. Database
Continuous Update Project Expert Panel
World Cancer Research Fund Secretariat

4. Continuous Update Project Database
Architecture
One central database
A Client/Server architecture
DB server
client application
client application
client application
Central Database (server)
 MySQL (high-performance relational DB)
 Internal structure designed to
accommodate the variety of publications
 Located on a dedicated server in Imperial
College London
Application (client)
 Java platform (compatible with most OS)
 Features to facilitate data extraction
 Supports retrieval of information in
several formats
 Written in a modular way allowing future
extensibility

5. Data Entry
 Relevant papers are identified
and the data extracted and
double checked by reviewers
Data are structured and stored
for further analysis
Data Export
 Data could be retrieved by a wide
range of factors
 Data could be exported in
MS Word tables
MS Excel Datasets
Ready for analysis
Usage
Continuous Update Project Database

6. Continuous Update Project Database

7. Screen data entry:
Study characteristics

8. Screen data entry:
Study results

9. Screen query builder

10. Data exported for analyses

11. Author, Year,
WCRF Code,
Country
Study name,
characteristics
Cases/
Study size
Follow-up
(years)
Case
ascertainment
Outcome Comparison
RR (95%CI)
Ptrend
Adjustment factors
Yates, 2014
oes00894
UK
EPIC-Norfolk,
Prospective Cohort,
Age: 39-74 years,
M/W
65/
24 066
15 years
Cancer and pathology
registries
Incidence, esophageal
adenocarc.,
gastroesophageal
junction
≥35 vs 18.5-<23 kg/m^2 4.95 (1.11-22.17) Age, gender
Hardikar, 2013
oes00875
USA
SBES,
Prospective Cohort,
Age: 30- years,
M/W
45/
411
5 months
Biopsy and follow up Incidence, oesophageal
adenocarcinoma
1.01 (0.94-1.10)
Age, cigarette smoking,
nsaid, gender
>35.1 vs 25 kg/m2 1.21 (0.32-4.48)
Chen, 2012
oes00843
China
CNRPCS,
Prospective Cohort,
Age: 40-79 years,
M
706/
142 214
15 years
Review of medical
records and death
certificates
Mortality, upper
aerodigestive cancer,
BMI 15 to <23.5kg/m²
Per 5 kgm^2 1.06 (0.83-1.37)
Age, alcohol
consumption, smoking
habbits, area, education
140/ BMI 23.5 to <35kg/m²
Per 5 kgm^2 0.87 (0.51-1.50)
ODoherty, 2012
oes00844
USA
NIH- AARP Diet and
Health Study,
Prospective Cohort,
Age: 50-71 years,
M/W,
Retired
253/
218 854
9 years
Linkage of the cohort
with database to state
cancer registries
Incidence, oesophageal
adenocarcinoma
≥35 vs <18.5 kg/m^2 2.11 (1.09-4.09)
Age, sex, alcohol
consumption, antacid
use, aspirin use,
cigarette smoking,
diabetes, ethnicity,
marital status, physical
activity, red meat intake,
education, fruit and
vegetable intake, non-steroidal
anti-inflammatory
drug use,
total energy, white meat
intake
Andreotti, 2010
oes00845
USA
AHS,
Prospective Cohort,
M,
Pesticide applicators and
their spouses
33/
67 947
10 years
Cancer registry Incidence, esophageal
cancer, men
≥35 vs 18.5-24.9 kg/m^2 Age, smoking status
Per 1 kgm^2 1.01 (0.94-1.10)
Oesophageal
8.1.1
Bmi
Data exported for tabulation

12. Number of articles in the
Continuous Update Project
(Last search: June 30, 2014)
0 200 400 600 800
Breast
Colorectal
Prostate
Lung
Stomach
Pancreas
Liver
Bladder
Endometrial
Ovary
Kidney
Oesophageal
Polyps
Gallbladder
2005 SLR
CUP
Prospective studies
Randomized controlled trials
0 20 40 60
Polyps
Lung
Stomach
Prostate
Colorectal
Breast
Bladder
Pancreas
Endometrial
Kidney
Ovary
Oesophageal
4230 218
Liver
Gallbladder

13. Number of articles in the
Continuous Update Project
database for selected items
(Last search: June 30, 2014)
0 200 400 600 800 1000 1200 1400 BMI 1600
Total alcoholic drinks
Alcohol (as ethanol)
Alcohol consumption
Energy intake
Fruits
Fish
Total fat (as nutrients)
Coffee
Weight
Vitamin C
Beta-carotene
Eggs
Height
Vegetables
Tea
Vitamin E
Saturated fatty acids
Red meat
Total protein
Dietary fibre
Vitamin A
Retinol
Milk
MUFA

14. Data analysis:
Statistical methods
Dose-response meta-analysis using generalized least-squares
for trend estimation (command GLST in Stata)

15. Data analysis:
Statistical methods
Stratified analyses, sensitivity analyses
Figure 16 Relative risk of oesophageal adenocarcinoma for 5 kg/m2
increase of BMI by exposure assessment methods
Author
Year
Sex
Self-reported
Abnet
Merry
Reeves
Subtotal (I-squared = 73.4%, p = 0.023)
.
2008
2007
2007
M/W
M/W
W
Measured
Hardikar
Steffen
Corley
Samanic
Engeland
Subtotal (I-squared = 0.0%, p = 0.446)
.
2013
2009
2008
2006
2004
M/W
M/W
M/W
M
M/W
Medical records
Lindblad
Subtotal (I-squared = .%, p = .)
.
2005
M/W
NOTE: Weights are from random effects analysis
per 5 kg/m2
RR (95% CI)
1.28 (1.13, 1.45)
1.93 (1.47, 2.59)
1.54 (1.26, 1.89)
1.52 (1.22, 1.89)
1.05 (0.73, 1.61)
1.54 (1.12, 2.10)
1.61 (1.22, 2.19)
1.56 (1.15, 2.10)
1.56 (1.39, 1.75)
1.53 (1.39, 1.67)
1.41 (1.13, 1.76)
1.41 (1.13, 1.76)
%
Weight
40.44
26.15
33.41
100.00
5.66
8.98
10.08
9.74
65.55
100.00
100.00
100.00
Study
Description
NIH- AARP
NLCS
MWS
SBES
EPIC
KPMCP
SCWC
Norwegian 1963-1989
GPRDC
.386 1 2.59

16. Statistical methods
Publication and related bias
Data analysis:
Exploratory analyses

17. Continuous Update Project Reports
http://www.wcrf.org/cancer_research/cup/key_findings/index.php

18. Breast cancer
Premenopause
Second Expert Report 2007
Continuous Update Project 2010

19. Breast cancer
Postmenopause
Second Expert Report 2007 Continuous Update Project 2010

20. Colorectal cancer
Second Expert Report 2007 Continuous Update Project 2011

21. Colorectal cancer
Dietary fibre dose-response per 10 g/d
.3 .5 .75 1 1.5 2
Relative R isk
Study
Relative Risk
(95% CI)
Fibre
Kabat, 2008 1.03 ( 0.85, 1.25)
Nomura, 2007 0.87 ( 0.81, 0.94)
Schatzkin, 2007 0.99 ( 0.87, 1.12)
Wakai, 2007 0.55 ( 0.33, 0.93)
McCarl, 2006 0.90 ( 0.83, 0.99)
Otani, 2006 0.82 ( 0.61, 1.10)
Shin, 2006 0.97 ( 0.61, 1.53)
Bingham, 2005 0.82 ( 0.74, 0.90)
Lin, 2005 0.82 ( 0.60, 1.12)
Michels, 2005, NHS 0.96 ( 0.78, 1.18)
Michels, 2005, HPFS 0.94 ( 0.80, 1.11)
Sanjoaquin, 2004 0.90 ( 0.65, 1.25)
Mai, 2003 0.98 ( 0.73, 1.31)
Terry, 2001 0.99 ( 0.72, 1.37)
Pietinen, 1999 1.00 ( 0.79, 1.27)
Heilbrun, 1989 0.94 ( 0.64, 1.40)
Overall 0.90 ( 0.86, 0.94)
1
.6 .8
Estimated RR
Dietary fibre, dose-response curve
0 10 20 30 40
Dietary fiber (g/day)
Best fitting fractional polynomial
95% confidence interval
Continuous Update Project Colorectal cancer report 2011 BMJ 2011;343:d6617 doi: 10.1136/bmj.d6617

22. Colorectal cancer
Fibre by food source
Fibre from fruits, dose-response per 10 g/d
.3 .5 .75 1 1.5 2
Relative R isk
Study
Relative Risk
(95% CI)
Nomura, 2007 0.88 ( 0.78, 0.99)
Schatzkin, 2007 1.11 ( 0.95, 1.28)
Wakai, 2007 1.90 ( 0.40, 9.04)
Bingham, 2005 0.63 ( 0.33, 1.19)
Lin, 2005 0.90 ( 0.31, 2.63)
Michels, 2005, NHS 0.76 ( 0.53, 1.08)
Michels, 2005, HPFS 0.83 ( 0.62, 1.11)
Mai, 2003 1.11 ( 0.64, 1.90)
Terry, 2001 0.97 ( 0.45, 2.09)
Overall 0.93 ( 0.82, 1.05)
Fibre from legumes, dose-response per 10 g/d
.01 .3 .5 .75 1 1.5 2 4
Relative Risk
Study
Relative Risk
(95% CI)
Schatzkin, 2007 0.85 ( 0.65, 1.11)
Bingham, 2005 1.09 ( 0.34, 3.53)
Lin, 2005 0.02 ( 0.00, 0.37)
Mai, 2003 0.53 ( 0.15, 1.86)
Overall 0.62 ( 0.27, 1.42)
Fibre from vegetables, dose-response per 10 g/d
.3 .5 .75 1 1.5 2
Relative R isk
Study
Relative Risk
(95% CI)
Nomura, 2007 0.93 ( 0.84, 1.03)
Schatzkin, 2007 1.04 ( 0.89, 1.21)
Wakai, 2007 0.71 ( 0.26, 1.91)
Bingham, 2005 0.78 ( 0.37, 1.64)
Lin, 2005 2.32 ( 0.35, 15.50)
Michels, 2005, HPFS 1.08 ( 0.83, 1.41)
Michels, 2005, NHS 1.10 ( 0.81, 1.51)
Mai, 2003 0.91 ( 0.48, 1.72)
Terry, 2001 3.15 ( 0.63, 15.64)
Overall 0.98 ( 0.91, 1.06)
Fibre from cereals, dose-response per 10 g/d
.3 .5 .75 1 1.5 2
Relative R isk
Study
Relative Risk
(95% CI)
Nomura, 2007 0.95 ( 0.84, 1.07)
Schatzkin, 2007 0.79 ( 0.67, 0.93)
Bingham, 2005 0.85 ( 0.58, 1.24)
Lin, 2005 0.94 ( 0.28, 3.12)
Michels, 2005, NHS 0.88 ( 0.63, 1.24)
Michels, 2005, HPFS 0.86 ( 0.66, 1.13)
Mai, 2003 1.01 ( 0.63, 1.61)
Terry, 2001 1.02 ( 0.73, 1.43)
Overall 0.90 ( 0.83, 0.97)
Continuous Update Project Colorectal cancer report 2011 BMJ 2011;343:d6617 doi: 10.1136/bmj.d6617

23. Pancreatic cancer
Second Expert Report 2007 Continuous Update Project 2012

24. Pancreatic cancer
Alcohol (as ethanol)
Fructose, dose-response per 25 g/day
Saturated fat, dose-response per 10 g/day

25. Endometrial cancer

26. Endometrial cancer
Coffee, dose-response per 1 cup/day
Glycaemic load, dose-response per 50 units/day
Sitting time, highest compared to lowest

27. Ovarian cancer

28. Ovarian cancer
BMI, dose-response per 5 units Height, dose-response per 5 cm

29. Breast Cancer Survivors

Final report to be published 2014,
outcomes mortality (all cause & breast
cancer) and second primary breast
cancer.

Talk on Friday 3 October

Poster

30. Thanks!
Continuous Update Project Team
Dagfinn Aune; Snieguole Vingeliene; Deborah Navarro Rosenblatt; Teresa Norat; Doris Chan;
Ana Rita Vieira, Leila Abar and Christophe Stevens (not in photo)
Darren Greenwood, University of Leeds, Statistical Advisor (not in photo)