2011 Progress Report: Childhood Leukemia International Consortium Studies

EPA Grant Number: R834511C001
Subproject: this is subproject number 001 , established and managed by the Center Director under grant R834511
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Center for Integrative Research on Childhood Leukemia and the Environment (CIRCLE)
Center Director: Buffler, Patricia
Title: Childhood Leukemia International Consortium Studies
Investigators: Buffler, Patricia , Metayer, Catherine
Institution: University of California - Berkeley
EPA Project Officer: Louie, Nica
Project Period: September 25, 2009 through September 24, 2015
Project Period Covered by this Report: September 25, 2010 through September 24,2011
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2009) RFA Text |  Recipients Lists
Research Category: Children's Health , Health

Objective:

The proposed new Children’'s Environmental Health Center based at the University of California, Berkeley is designed to examine the effects of in utero and early life exposure to potentially carcinogenic chemicals present in homes (i.e., pesticides, tobacco-related contaminants, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs)), and genetic and epigenetic factors and their interplay in the development of childhood leukemia. The Center, referred to as Center for Interdisciplinary Research on Childhood Leukemia and the Environment (CIRCLE), includes three research projects and two cores. This report focuses on the first project.

Project 1: Childhood Leukemia International Consortium Studies will identify the exposures to the most relevant time periods and childhood leukemia subtypes and identify important genetic polymorphisms that can modify the association between childhood leukemia and parental tobacco smoking or home pesticide exposure by pooling data from 19 studies worldwide.

Progress Summary:

Specific Aim 1: Pool data elements collected from 14 CLIC case-control studies in 10 countries

More than 40 participants attended the 2010 CLIC Annual Meeting held in Boston, MA, October 19-20. The work proposed under the current award was presented at the meeting and well received. Following the meeting, the CLIC Management Group (chaired by P. Buffler, Director of CIRCLE) held regular (monthly and bimonthly conference calls to discuss issues related to data pooling and data directories, progress on proposed pooled analyses, new applications for CLIC individual and study memberships, and organization of the CLIC annual meeting.

The procedures for requesting data have been revised by the Data Pooling Core Logistics Group and the next call for Expressions of Interest (EOI) for CLIC PIs to propose pooled analyses is June 1, 2011. The lead roles for pooled analyses in the current award are presented in Table 1. The affiliated institution of Dr. Helen Bailey is the Telethon Institute for Child Health Research, West Perth, Australia. Dr. Bailey will be conducting the pooled analyses at the International Agency for Research on Cancer (IARC) as part of her post-doctoral position under the supervision of Dr. Joachim Schuz (Head, Section of Environment and Radiation, IARC).

The survey to assess quality and completeness of cytogenetic data in CLIC studies is under review by two CLIC molecular biology members (Drs. Zhang and Pombo-de-Oliveira), and will be circulated to all CLIC PIs. Additionally, a survey of available genetic data and biospecimens is underway.

Specific Aim 2: Conduct descriptive analyses to assess geographical differences in the frequency of leukemia subtypes defined by age, immunophenotype and cytogenetics, and assess possible sources for geographical differences

No activities were conducted on this aim in Year 2 (Waiting to obtain data).

Specific Aim 3: Assess the association between maternal/paternal smoking or home pesticide exposures and childhood leukemia during different time periods (prenatal, during pregnancy, and postnatal) stratified by histologic, immunophenotypic, and cytogenetic subtypes

No activities were conducted on this aim in Year 2 (waiting to obtain data).

Specific Aim 4: Examine the influence of genetic variation on the association between parental smoking or home pesticide exposures and childhood leukemia by histologic, immunophenotypic and cytogenetic subtypes

No activities were conducted on this aim in Year 2 (waiting to obtain data).

Specific Aim 5: Maintain the CLIC website http://clic.berkeley.edu to facilitate communication among CLIC members and outside communities

The CLIC website has been upgraded from a collection of static html pages to a dynamic site, which can be updated by approved users. A “"member’s only"” section has been created, accessible via a user authentication process, which includes announcements of activities, events and forums, and a document posting and tracking system. Dedicated sections for CLIC Interest Groups, Logistic Groups, and Working Groups have been added where group members can post messages and documents to facilitate communication and exchange of ideas. Approved members have viewing, editing, or administrative rights within these groups. These features of the CLIC website currently are under testing and will be opened for CLIC member use (members will be invited to obtain user names) by June 2011. Other features are in development.

Significance

Leukemia is the most common type of childhood cancer. About 2,400 cases of childhood leukemia (ages 0-14 years) are diagnosed annually in the United States. The etiology of childhood leukemia is complex; confirmed clinical and epidemiologic associations explain less than 10% of childhood leukemia incidence. Project 1 is the first epidemiologic study to date that proposes to collaborate with a large international group of investigators in order to examine ubiquitous environmental exposures (i.e., tobacco smoking and residential pesticides) that may be causally associated with the most frequent cancer in children. Pooling data from 14 case-control studies presents a unique opportunity to fully investigate the critical periods of exposures to these contaminants and the possible modifying effects of metabolizing genes in the etiology of childhood, and to examine rare and less-studied childhood leukemia types like acute myeloid leukemia and other cytogenetic subgroups.

Future Activities:

Specific Aim 1: Continue data pooling. Complete inventory of cytogenetic data. Continue development of meta-database. Organize the 2011 CLIC meeting in Barcelona (September 16-18) in conjunction with the conferences of the International Society for Environmental Epidemiology (ISEE) and the International Childhood Cancer Cohort Consortium (I4C).

Specific Aim 2: Start statistical analyses.

Specific Aim 3: Start statistical analyses.

Specific Aim 4: Assess availability of genetic data for pooled analyses.

Specific Aim 5: Continue website maintenance and incorporate meta-database to allow web-based inventory of questionnaire and biospecimen data.

Progress and Final Reports:

Original Abstract
  • 2010
  • 2012
  • 2013
  • 2014
  • Final

  • Main Center Abstract and Reports:

    R834511    Center for Integrative Research on Childhood Leukemia and the Environment (CIRCLE)

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R834511C001 Childhood Leukemia International Consortium Studies
    R834511C002 Exposure Assessment for Childhood Leukemia
    R834511C003 Prenatal Exposures, DNA Methylation & Childhood Leukemia