Stomach cancer Pooling (StoP) Project

StoP Group

 

 

MINUTES OF THE FIRST PROJECT MEETING – JUNE 11, 2013 –

ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI, MILAN, ITALY

 

Participants:

Nuria Aragones, Instituto de Salud Carlos III, Madrid, Spain; naragones@isciii.es
Andrea Bellavia, Karolinska Institutet, Stockholm, Sweden; andrea.bellavia@ki.se
Paola Bertuccio, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; paola.bertuccio@marionegri.it
Stefania Boccia, Catholic University of Sacred Heart, Rome, Italy; sboccia@rm.unicatt.it
Cristina Bosetti, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; cristina.bosetti@marionegri.it
Gemma Castano Vinyals, Centre for Research in Environmental Epidemiology, Barcelona, Spain; gcastano@creal.cat
Monica Ferraroni, University of Milan, Italy; monica.ferraroni@unimi.it
Carlotta Galeone, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; carlotta.galeone@marionegri.it
Carlo La Vecchia, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; carlo.lavecchia@marionegri.it
Nuno Lunet, University of Porto, Portugal; nlunet@med.up.pt
Keitaro Matsuo, Aichi Cancer Center Research Institute, Nagoya, Japan; kmatsuo@aichi-cc.jp
Dmitry Maximovich, Russian N.N. Blokhin Cancer Research Centre, Moscow, Russia; dmax@crc.umos.ru
Lina Mu, University at Buffalo, USA; linamu@buffalo.edu
Joshua Muscat, Penn State University, Hershey, USA; jmuscat@hmc.psu.edu
Eva Negri, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; eva.negri@marionegri.it
Claudio Pelucchi, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; claudio.pelucchi@marionegri.it
Delphine Praud, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; delphine.praud@marionegri.it
Tiziana Rosso, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; tiziana.rosso@marionegri.it
Matteo Rota, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; matteo.rota@marionegri.it
Zuo-Feng Zhang, University of California, Los Angeles, USA; zfzhang@ucla.edu

Participation by conference call:

Paolo Boffetta, Mount Sinai School of Medicine, New York, USA; paolo.boffetta@mssm.edu

 

  1. 1.      Opening, introduction (C La Vecchia/ZF Zhang)

Carlo La Vecchia welcomed all participants and opened the meeting.

 

  1. 2.      Study reports (various participants)

a)    Each PI/study referent presented his/her study (or studies) participating to the StoP Project. Paola Bertuccio presented briefly the studies whose PIs could not be present at the meeting.

b)   Zuo-Feng Zhang introduced two new studies that will be included in the project: the Yangzhong study (China, 133 cases of gastric cancer [GC], 166 subjects with chronic gastritis, and 433 controls) and the MSKCC study (USA, 67 cases of cardia GC, 67 of distal GC, and 67 controls); and Keitaro Matsuo introduced two other new studies that might be included in the near future, i.e. the HERPACC I study (2667 cases) and the HERPACC III study (still ongoing, over 1000 cases).

c)    Nuria Aragones reported that the database of the Spanish study will be ready in the next few months.

d)   Andrea Bellavia reported that the database of the Swedish study (PI: Nicola Orsini) is almost ready.

e)    With reference to other potential participating/collaborating studies, Keitaro Matsuo noted that the Asia Cohort Consortium (ACC) has mortality (and not incidence) data on GC. For this cancer, however, incidence and mortality do not show major differences.

 

  1. 3.       Update of work in progress (C Pelucchi/C Galeone)

Claudio Pelucchi reported the early achievements of the project and summarized the current situation with reference to:

a)    study inclusion (21 studies from 11 countries, for a total of about 9000 cases);

b)   data collection (full datasets already available for 11 studies – and 4 others were provided at the meeting, for a total of 15 datasets);

c)    no. of GC cases by subsite (out of 9 studies, 579 with GC of the cardia, 409 of the corpus/fundus, 451 of the pylorus, 2949 undefined) and histological type (out of 9 studies, 669 with intestinal type, 344 with diffuse type, 3375 undefined);

d)   data harmonization (started for 6 studies, completed for 2).

Carlotta Galeone introduced the StoP working group at the Mario Negri Institute, and updated on project procedures, email and website (to be developed). Graphic proposals for a project logo are welcome.

 

  1. 4.      Problems arising during data pooling (D Praud)

Delphine Praud reported on the list of core variables selected for standardization and the methods used for data harmonization. In particular, she underlined a few specific problems that emerged in the early phases of the harmonization process, including standardization of:

a)    subsite and histological type of GC, as studies use different classification methods; it was decided that the project should not only separate cardia from noncardia GC, but also differentiate the noncardia subsites (i.e., corpus, fundus, pylorus, etc.), according to ICD-10 classification. Also, the project aims at investigating separately intestinal and diffuse histotypes of GC, though the validity of information might be questionable when a surgical specimen is absent, since the two histotypes show relevant structural, and possibly also aetiological, differences; it was suggested to involve in the project an expert in pathology to assist with histological issues. Nuno Lunet proposed to contact Fatima Carneiro;

b)   social class, defined according to either education (study-specific cutoffs), income or occupation;

c)    alcohol drinking in grams/day, as studies used different measurement units. It was decided to use a standard transformation of 1 drink=12 grams, except for Japan. It was specified that only subjects who stopped drinking since at least one year will be considered ex-drinkers.

Lina Mu asked to include pack-years among the variables in the “smoking” card.

 

  1. 5.      Statistical methods (M Rota)

Matteo Rota presented the statistical plan for data analyses. Two main methods to conduct the analyses were proposed:

a)    a joint random-effects logistic regression

b)   a two-stage random effects model

The latter is better for various reasons, including its performances in simulation studies and the possibility to incorporate study-specific confounders in the first stage. Eva Negri supported this method, though she noted that it was criticized in other studies because it does not allow to examine the interactions between variables.

 

  1. 6.      H. pylori infection (N Lunet)

a)      Whenever information will be available on the strain of H. pylori, it will be important to examine the possible confounding / effect modification role of strains with different virulence.

b)      With further reference to geographic area, Nuno Lunet specified that the analyses of cardia cancer will have to be stratified according to low- / high-risk area, since cardia cancers are easily misclassified between esophageal and gastric cancers. Socio-economic status is also a major confounder of the association between H. pylori and GC, that has to be taken into account separately in low- / high-risk areas. In fact, socio-economic status is also a surrogate for the duration of H. pylori infection (i.e., in low risk areas, the infection is less common and generally occurs during childhood, whereas in high risk areas the infection is common in adolescents and adults, too). Nuria Aragones noted that – if available – a covariate for education/social class of the parents would be more appropriate in this context.

c)      In conclusion, the role of H. pylori will be carefully examined and taken into account in all the subprojects, whenever available.

  1. 7.      First risk factors for pooled analyses (E Negri)

a)      The first subprojects planned are those on tobacco, alcohol and socio-economic status in relation to GC risk. According to IARC, there is sufficient evidence for a role of cigarette, pipe and cigar smoking in the aetiology of GC. Tobacco use was selected as the first risk factor to examine because i) it is likely that all studies will have this information; ii) it is a standard variable, relatively easy to analyse; iii) there are still several aspects related to tobacco that deserve analysis and quantification of risks.

b)      The same rationale applies to alcohol drinking, too. Meta-analyses of published studies suggest that alcohol is not associated with cardia GC and mildly positively related with noncardia GC, particularly at elevated doses of consumption. Keitaro Matsuo mentioned the role of polymorphisms of alcohol metabolism (i.e., ADH, ALDH), that is particularly relevant in East Asia, where in fact several studies reported an association between alcohol and GC. Lina Mu referred of a potential interaction with green tea, that might confer some protection to alcohol drinkers, and can be examined in our study.

c)       As already noted in the previous presentation by Nuno Lunet, investigation of the effects of socio-economic status will be more complex. Analyses will need to take into due consideration several different co-factors in various geographical areas. For example, Lina Mu reminded that in China low social class is associated to malnutrition and high consumption of salt-preserved foods. Stefania Boccia proposed to use, among other indicators of social class, the Relative Index of Inequality (RII), developed by the group of Prof. JP Mackenbach, that is increasingly used in epidemiological studies.

 

AFTERNOON SESSION

  1. 8.      Proposals for other risk factors (N Lunet / S Boccia)

Everyone was invited to propose issues to investigate in future subprojects.

a)      Nuno Lunet is interested to analyze in-depth the role of H. pylori and particularly of its strains.

b)      Stefania Boccia aims to address the role of height in relation to GC risk. The latter factor is strongly related to socio-economic status, thus a major issue will be to disentangle their separate effects. Also, H. pylori infection during childhood age has an influence on adult height, thus Nuno and Stefania will have to collaborate for these subprojects.

c)      Nuria Aragones expressed her interest for a subproject to investigate the geographical variation of GC incidence.

d)     Nuno Lunet proposed a methodological paper aimed to compare results between a study-level meta-analysis and an individual-level pooled-analysis of data of the consortium, on a specific topic yet to be defined. These results will also be compared to already published meta-analyses on the same topic. This will permit to address the role of bias (such as publication bias) in meta-analysis.

The StoP dataset v.1.0 (including harmonized data of all the studies that will provide their datasets by September 2013), will approximately be ready at the end of 2013. It was agreed that, by the end of this year, the full list of variables that were standardized and included in the database will be circulated to all PIs, in order to facilitate proposals for subprojects.

 

  1. 9.      Database of biologic / genetic variables (S Boccia / N Lunet / K Matsuo)

Stefania Boccia invited the PIs of those studies with biological materials to provide detailed information on the number of samples collected (separately for cases and controls), and the type of materials collected, i.e., DNA extracted from blood samples (or just stored blood samples); serum; plasma; frozen tumoural tissue; paraffin-embedded tumoural tissue; any other biological material. In order to understand the potential for this section of the project, as well as to define the aims, it is important to clarify the current situation of which biologic materials are available from the participating studies.

Paolo Boffetta agreed that an inventory of biological materials is needed, also in consideration of a possible collaboration with NCI for a replication study. On the other hand, our sample might not allow to conduct an own GWAS study. Once the situation will be clear, Paolo Boffetta, Stefania Boccia, Nuno Lunet and Keitaro Matsuo will have a conference call with Phil Taylor (NCI).

Evidences from GWAS on potential genes involved in the risk of GC include:

a)      Mucin 1

b)      PSCA

c)      E-cadherin

 

  1. 10.  Collaboration with the Asia Cohort Consortium (P Boffetta)

Paolo Boffetta updated on his contacts with leaders of the ACC. The ACC includes about 900 cases of GC from China and Korea, 2600 from Japan and 50 from India and Bangladesh. Paolo and Keitaro Matsuo will prepare a proposal to be submitted to the executive committee of the ACC. Possible types of collaboration are:

a)      to conduct parallel analyses on a number of risk factors in the StoP and ACC consortia;

b)      to work separately in the first-stage analyses, and then pool all the data of the StoP and ACC consortia together in second-stage analyses;

c)      to obtain data from the ACC and include them in the StoP Project.

 

  1. 11.  Grant applications (all participants)

Besides applications to the Italian Ministry of Health and the Italian Association for Cancer Research (already submitted, results will be made available at the end of 2013), other ideas for potential applications were:

a)      To contact a green tea company (assuring however that the study will fully maintain its independence);

b)      To apply to one or more of the following US foundations, proposed by Paolo Boffetta, i.e., the DeGregorio Family Foundation (http://www.degregorio.org/wp/), the Debbie’s Dream Foundation (http://debbiesdream.org/portal/web/guest/home), or the Gastric Cancer Foundation (http://www.gastriccancer.org/). The latter seems to be most appropriate one with reference to cancer prevention/epidemiology;

c)      To submit a proposal at the European Cooperation in Science and Technology (COST) Actions, that provides funding for research networks.

Zuo-Feng Zhang will contact the Gastric Cancer Foundation to propose the StoP consortium. If the Foundation will demonstrate interest for our consortium, we will then develop an ad hoc proposal to submit. The next deadline for COST Actions is 27 September 2013.

 

  1. 12.  Formal aspects (E Negri)

Eva Negri presented two draft versions of the authorship policies. These were adapted from those of the INHANCE Consortium. After discussion, all participants agreed to adopt the same version as INHANCE, i.e., to include up to two authors from each study contributing data, plus up to five authors for the “writing team”.

A proposal form to apply for subprojects was also presented. All the participants approved it.

 

  1. 13.  Publications (C La Vecchia / S Boccia)

a)      A draft of the project description paper will be circulated in July/September, as soon as the list of studies participating to the StoP dataset v.1.0 will be defined. This manuscript will be submitted to the European Journal of Cancer Prevention, the official journal of the European Cancer Prevention organization, that provided funding for the Milan meeting;

b)      A number of publications will be based on the StoP dataset v.1.0, but we agreed that the database will be further expanded in the near future to include other studies wishing to participate (and other variables of interest);

c)      Stefania Boccia is Lead Guest Editor of a special issue on gastric cancer of “Gastroenterology Research and Practice”. She introduced the issue and circulated a call for papers. Submission of manuscript from the consortium PIs are welcome;

d)     Joshua Muscat proposed to write a series of summaries of the StoP publications, to be submitted yearly or twice-yearly to a gastroenterology journal.

  1. 14.  Closing (C La Vecchia)

Carlo La Vecchia thanked all participants for their contributions and for the fruitful meeting. Next year meeting will possibly be held in Rome together with the INHANCE and ILCCO consortia annual meetings.

 

 

 

ACTION POINTS (subject(s) in charge of):

  • To develop the project website (Mario Negri team)
  • To propose for a project logo (anyone interested)
  • To contact an expert in pathology (Fatima Carneiro?) to assist with histological issues (N Lunet)
  • To add pack-years among the standardization variables in the “smoking” card (Mario Negri team)
  • To provide detailed information on the number of biological samples collected (separately for cases and controls), and the type of materials collected, i.e., DNA extracted from blood samples (or just stored blood samples); serum; plasma; frozen tumoural tissue; paraffin-embedded tumoural tissue; any other biological material (PIs of those studies with biological materials)
  • To prepare a proposal to be submitted to the executive committee of the ACC (P Boffetta / K Matsuo)
  • To contact the Gastric Cancer Foundation to propose the StoP consortium (ZF Zhang)
  • To prepare and circulate a draft of the project description paper (C Pelucchi / S Boccia)
  • All the studies that want to participate to the first subprojects, thus contributing data to the StoP dataset v.1.0, should provide their datasets and questionnaires by the end of September 2013 (any interested PI/referent)

 

Table   1. MasterTable tracking   contacts and progresses with studies that have already provided the dataset   (ID: 1-15) or have agreed to participate to the StoP Project

Study ID

Country

PI

Co-PI / contact person (if different from PI)

Date 1st Contact

Study Description Form (SDF)

Data Transfer Agreement (DTA)

Dataset

Study Questionnaire

Harmonisation

1

Italy

C. La Vecchia

X

X

X

X

2

China

Jinfu Hu

23/07/2012

X

X

X

X

STARTED

3

Italy

E. Negri

X

X

X

X

STARTED

4

Italy

S. Boccia

15/11/2012

X

X

X

X

5

Italy

D. Palli

M. Ferraroni

23/07/2012

X

X

X

X

X

6

Greece

D. Trichopoulous

P. Lagiou

23/07/2012

X

X

X

X

STARTED

7

Canada

K. Johnson

J. Hu

23/07/2012

X

X

X

X

X

8

China

L. Mu

23/07/2012

X

X

X

X

STARTED

9

Russia

D. Zaridze

D. Maximovich

23/07/2012

X

X

X

X

10

Iran

R. Malekzadeh

M. Derakhshan (REF IJC 2009)

15/01/2013

X

X

X

11

Iran

R. Malekzadeh

M. Derakhshan (REF CCC 2011)

15/01/2013

X

X

X

12

China

Z.F.Zhang

G.P. Yu (REF APJCP 2005)

25/01/2013

X

X

13

China

Z.F.Zhang

(REF IJC 2001)

25/01/2013

X

14

USA

Z.F.Zhang

(REF CDP 1999)

25/01/2013

X

15

Japan

K. Matsuo

H. Ito

23/07/2012

X

X

X

Portugal

N. Lunet

X

X

USA

J. Muscat

23/07/2012

X

X

Iran

R. Malekzadeh

M. Derakhshan (REF Gut 2008)

15/01/2013

X

X

Spain

N. Aragones

M. Kogevinas/G. Castano Vinyals

15/02/2013

X

Sweden

0. Nyren

W. Ye

12/04/2013

X

Sweden

N. Orsini

A. Wolk/A. Bellavia

05/04/2013

X

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