Continuous Update Project: Database update and systematic literature reviewTeresa NoratPrincipal Investigator Continuous Update Project, Imperial College London

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)

Database

Continuous Update Project Expert PanelWorld Cancer Research Fund Secretariat

Architecture

DB server

client application

client application

client application

A Client/Server architectureCentral Database (server)

Application (client)

MySQL (high-performance relational DB) Internal structure designed to accommodate the variety of publications

Located on a dedicated server in Imperial College London

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

Continuous Update Project Database

One central database

Data Entry

Data Export

Relevant papers are identified and the data extracted and double checked by reviewers

Data are structured and stored for further analysis

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

Continuous Update Project Database

Screen data entry: Study characteristics

Screen data entry: Study results

Screen query builder

Data exported for analyses

Author, Year, WCRF Code,

Country

Study name, characteristics

Cases/Study sizeFollow-up

(years)

Case ascertainment

Outcome ComparisonRR (95%CI)

PtrendAdjustment factors

Yates, 2014oes00894

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, 2013oes00875

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, 2012oes00843

China

CNRPCS, Prospective Cohort, Age: 40-79 years,

M

706/142 21415 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/m²Per 5 kgm^2 0.87 (0.51-1.50)  

ODoherty, 2012oes00844

USA

NIH- AARP Diet and Health Study,

Prospective Cohort, Age: 50-71 years,

M/W, Retired

253/218 8549 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, 2010oes00845

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

Number of articles in the Continuous Update Project

(Last search: June 30, 2014)

Breast

Colorectal

Prostate

Lung

Stomach

Pancreas

Liver

Bladder

Endometrial

Ovary

Kidney

Oesophageal

Polyps

Gallbladder

0 100 200 300 400 500 600 700 800

2005 SLRCUP

Prospective studies

Polyps

Lung

Stomach

Prostate

Colorectal

Breast

Bladder

Pancreas

Endometrial

Kidney

Ovary

Oesophageal

Liver

Gallbladder

0 5 10 15 20 25 30 35 40 45 50

Randomized controlled trials

4230 218

BMI

Total alcoholic drinks

Alcohol (as ethanol)

Alcohol consumption

Energy intake

Fruits

Fish

Total fat (as nutrients)

CoffeeWeight

Vitamin C

Beta-carotene

Eggs

Height

Vegetables

Tea

Vitamin ESaturated fatty acids

Red meat

Total proteinDietary fibre

Vitamin A

Retinol

Milk

MUFA

0 200 400 600 800 1000 1200 1400 1600

Number of articles in the Continuous Update Project database for selected items

(Last search: June 30, 2014)

Data analysis:Statistical methods

Dose-response meta-analysis using generalized least-squares for trend estimation (command GLST in Stata)

Data analysis:Statistical methods

Stratified analyses, sensitivity analyses

NOTE: Weights are from random effects analysis

.

.

.

Self-reported

Abnet

Merry

Reeves

Subtotal (I-squared = 73.4%, p = 0.023)

Measured

Hardikar

Steffen

Corley

Samanic

Engeland

Subtotal (I-squared = 0.0%, p = 0.446)

Medical records

Lindblad

Subtotal (I-squared = .%, p = .)

Author

2008

2007

2007

2013

2009

2008

2006

2004

2005

Year

M/W

M/W

W

M/W

M/W

M/W

M

M/W

M/W

Sex

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)

RR (95% CI)

per 5 kg/m2

40.44

26.15

33.41

100.00

5.66

8.98

10.08

9.74

65.55

100.00

100.00

100.00

Weight

%

NIH- AARP

NLCS

MWS

SBES

EPIC

KPMCP

SCWC

Norwegian 1963-1989

GPRDC

Description

Study

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)

RR (95% CI)

per 5 kg/m2

40.44

26.15

33.41

100.00

5.66

8.98

10.08

9.74

65.55

100.00

100.00

100.00

Weight

%

1.386 1 2.59

Figure 16 Relative risk of oesophageal adenocarcinoma for 5 kg/m2 increase of BMI by exposure assessment methods

Publication and related biasExploratory analyses

Data analysis:Statistical methods

http://www.wcrf.org/cancer_research/cup/key_findings/index.php

Continuous Update Project Reports

Breast cancer Premenopause

Second Expert Report 2007Continuous Update Project 2010

Second Expert Report 2007 Continuous Update Project 2010

Breast cancer Postmenopause

Colorectal cancer

Second Expert Report 2007 Continuous Update Project 2011

Relative Risk .3 .5 .75 1 1.5 2

Study Relative Risk (95% CI)

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)

Dietary fibre dose-response per 10 g/d

.6.8

1E

stim

ated

RR

0 10 20 30 40Dietary fiber (g/day)

Best fitting fractional polynomial95% confidence interval

Dietary fibre, dose-response curve

Continuous Update Project Colorectal cancer report 2011 BMJ 2011;343:d6617 doi: 10.1136/bmj.d6617

Colorectal cancerFibre

Relative Risk .3 .5 .75 1 1.5 2

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

Relative Risk .01 .3 .5 .75 1 1.5 2 4

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 fruits, dose-response per 10 g/d

Relative Risk .3 .5 .75 1 1.5 2

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 vegetables, dose-response per 10 g/d

Fibre from cereals, dose-response per 10 g/d

Relative Risk .3 .5 .75 1 1.5 2

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

Colorectal cancerFibre by food source

Continuous Update Project 2012Second Expert Report 2007

Pancreatic cancer

Pancreatic cancer

Alcohol (as ethanol)Fructose, dose-response per 25

g/day

Saturated fat, dose-response per 10 g/day

Endometrial cancer

Coffee, dose-response per 1 cup/day

Glycaemic load, dose-response per 50 units/day

Sitting time, highest compared to lowest

Endometrial cancer

Ovarian cancer

Ovarian cancer

BMI, dose-response per 5 units Height, dose-response per 5 cm

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

Continuous Update Project TeamDagfinn 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)

Thanks!