Childhood Leukemia International Consortium (CLIC)

1. Childhood Leukemia International Consortium (CLIC) Helen Bailey Post Doctoral Fellow International Agency for Research on Cancer WEBSITE: HTTPS://CLIC.BERKELEY.EDU CLIC_CENTRALOFFICE@BERKELEY.EDU

2. History of CLIC The Children with Cancer UK, the National Cancer Institute, the National Institutes of Environ-mental Health Sciences (NIEHS), and Environ-mental Protection Agency (EPA), US and the Cancer Council Western Australia have provided support for CLIC organization and/or pooled analyses.

3. Mission of CLIC • Develop and support collaborations between scientists involved in CL research to accelerate knowledge on factors that influence the risk of childhood leukemia through epidemiological studies and related research. • Encourage free exchange of results (published or unpublished) and ideas in a collegial environment without fear of competition.

4. Map of Childhood Leukemia Studies participating in CLIC 18, 19 12,13,14,15 17 8,9 16 1 20 5 21 2, 3 4 22 6 7 10,11 23 24 Principal Investigators/designated co-investigators, study area (from left to right): 1) Beth Mueller, Parveen Bhatti, Washington State, USA; 2) Patricia Buffler, Catherine Metayer, California State, USA; 3) Julia Heck, California State, USA; 4) Michael Scheurer, Melissa Bondy, Texas State, USA; 5) Logan Spector, USA; 6) Juan Manuel Mejía-Arangure, Mexico;7) Ana Mariá Mora, Costa Rica; 8) Claire Infante-Rivard, Quebec, Canada; 9) Daniel Sinnett, Quebec, Canada; 10) Maria Pombo-de-Oliveira, Sergio Koifman, Brazil; 11) Victor Wünsch Filho, São Paulo Brazil; 12) Eve Roman, Jill Simpson, UK; 13) Jill Birch, Malcolm Taylor, Manchester, UK; 14) Michael Murphy, UK; 15) Richard McNally, Northern England,UK; 16) Jacqueline Clavel, France; 17) Joachim Schüz, Peter Kaatsch, Germany; 18) Mats Heyman, Nordic Countries; 19) Julia Heck, Denmark; 20) Corrado Magnani, Italy; 21) Eleni Petridou, Nick Dissypris, Greece; 22) Sameera Ezzat, Egypt; 23) Elizabeth Milne, Bruce Armstrong, Australia; 24) John Dockerty, New Zealand.

5. Outstanding Research Questions • What are the critical windows of exposure? • What are the “environmental” (or non-genetic) risk factors for rarer childhood leukemia subtypes like AML, APL, T-cell ALL? • What risk factors are specific to childhood leukemia cytogenetic/molecular subtypes of ALL and AML, or other tumor characteristics? • What role does genetics play in CL etiology? • What is the contribution of gene-environment (GxE) interaction?

6. Summary of CLIC Member Studies • As of 2012, CLIC has 18 Principal Investigators (PIs) representing 22 childhood leukemia studies from mid 1970’s to present (2013 – additional 6 studies, not included in tables) • ~50% of the studies have biospecimens

7. Organization of the CLIC

8. CLIC Core Logistics Groups Core Logistics Groups advise and facilitate cross-cutting issues within the consortium. There are four groups.

9. CLIC Interest Groups The Interest Groups will promote collaborative projects in specific areas of childhood leukemia research. There are nine Interest Groups in CLIC.

10. CLIC Procedures

11. CLIC Working Groups – Pooled Analyses

12. Challenges • Specificity of studies regarding prevalence of exposure, design, confounders (e.g. socio-economic status, ethnicity, etc.) • Meta-data analyses vs. pooling of raw data • Recognize potential for selection bias in observational studies that require data access, subject consent, and importance of assessing the representativeness of study participants • Data harmonization

13. “Lessons Learned” • FUNDING is imperative to support a consortium. • Regular communication and timely feedback between steering committee members and PIs allow for accountability and progress. • In person meetings are invaluable. • Importance of flexibility.

14. Opportunities of Collaborations with the International Childhood Cancer Cohort Consortium (I4C) • Exchanges of ideas • Genetic, epigenetic and tumor biology studies • Exposure assessment • Ethical issues • Emerging hypotheses • Exchanges of procedures • Standardize data • Develop background information on exposure by country, time and activity patterns.

15. Publications Metayer C, Milne E, Clavel J, Infante-Rivard C, Petridou E, Taylor M, Schuz J, Spector LG, Dockerty JD, Magnani C, Pombo-de-Oliveira MS, Sinnett D, Murphy M, Roman E, Monge P, Ezzat S, Mueller BA, Scheurer ME, Armstrong BK, Birch J, Kaatsch P, Koifman S, Lightfoot T, Bhatti P, Bondy ML, Rudant J, O'Neill K, Miligi L, Dessypris N, Kang AY, Buffler PA. The Childhood Leukemia International Consortium. Cancer Epidemiology 2013. Milne E, Greenop KR, Metayer C, Schuz J, Petridou E, Pombo-de-Oliveira MS, Infante-Rivard C, Roman E, Dockerty JD, Spector LG, Koifman S, Orsi L, Rudant J, Dessypris N, Simpson J, Lightfoot T, Kaatsch P, Baka M, Faro A, Armstrong BK, Clavel J, Buffler PA. Fetal growth and childhood acute lymphoblastic leukemia: Findings from the Childhood Leukemia International Consortium (CLIC). International Journal of Cancer 2013.

16. Acknowledgements • Families of CLIC Member Studies • CLIC Coordination Group (Principal Investigators) and Management Group • Other CLIC Collaborators (Researchers, Clinicians, Advisors) • Our sponsors at the National Cancer Institute US, Children with Cancer UK, National Institute of Environmental Health Sciences (NIEHS) US, Environmental Protection Agency (EPA) US, Telethon Institute for Child Health Research, Australia, the Alex’s Lemonade Stand Foundation for Childhood Cancer (ALSF)US

17. Thank you! CLIC is an open consortium and welcomes individuals interested in childhood leukemia research. Membership applications and other CLIC guidelines can be found online at the CLIC website, https: clic.berkeley.edu. If you have any questions regarding the Consortium and/or difficulty accessing any of the documents, please contact Alice Kang at clic_centraloffice@berkeley.edu.