Continuous Update Project: Database update and systematic literature reviewTeresa Norat

Principal 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 Panel

World 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 size

Follow-up

(years)

Case

ascertainmentOutcome Comparison

RR (95%CI)

PtrendAdjustment 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

adenocarcinoma1.01 (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/m²Per 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)

Oesophageal8.1.1

Bmi

Data exported for tabulation

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

0 20 40 60

Polyps

Lung

Stomach

Prostate

Colorectal

Breast

Bladder

Pancreas

Endometrial

Kidney

Ovary

Oesophageal

Liver

Gallbladder

Randomized controlled trials

4230 218

0 200 400 600 800 1000 1200 1400 1600BMI

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

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 methodsStratified 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

1

Est

imat

ed R

R

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

Best fitting fractional polynomial

95% confidence interval

Dietary fibre, dose-response curve

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

Colorectal cancer

Fibre

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 cancer

Fibre 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 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)

Thanks!