Birth Defects and Cancer: The Intersection of Genes and Prenatal Exposures

September 10-11, 2012
Hyatt Regency - Atlanta, Georgia

(The workshop is a pre-meeting to the Children's Oncology Group [COG] meeting that
will be held at this same location. The COG meeting is September 11-14, 2012.)


Overview

Expansion of research efforts in understanding how early-life events/factors affect cancer risk has not been adequately undertaken for several reasons, including methodological challenges. Childhood cancers are rare, and risk of developing a cancer before age 20 is approximately 3 per 1,000. Most pediatric cancers are sporadic, non-familial events. However, pediatric cancer may also occur in a child with a cancer-predisposing genetic condition (e.g., families with neurofibromatosis type 1, Li-Fraumeni syndrome, familial hereditary retinoblastoma).

Despite the high risks of cancer occurrence in children from such families, not every child develops pediatric cancer. Childhood cancers may also occur in families with children who have chromosomal and non-chromosomal birth defects. Such co-occurrence may be due to underlying known genetic conditions, those not as yet identified, and possibly to unidentified environmental factors. This association between cancer and birth defects may be due to gene-gene or gene-environment interactions. From the developmental biology perspective, the etiology of birth defects and cancer share a common nexus in the genetic pathways governing signal transduction pathways and cell growth. Epidemiologic and genetic investigations of this association may provide new insights into the etiology of these diseases and adult-onset disease.

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Purpose

The objective of the workshop is to bring together experts/scientists working on birth defects and cancer to address the intersection of childhood cancer and birth defects, including the influence of prenatal exposures and genetic factors. The workshop will bring together a multidisciplinary team of experts to assess progress made and to prioritize research gaps.

In this workshop, experts will present their perspectives on major facets of birth defects and cancer research. Relatively limited investigations have focused on the intersection of genes and prenatal exposures and even fewer have focused on periconceptional or preconception exposures that may predispose to occurrence of:

  1. Birth defects,
  2. Pediatric cancers arising in children with birth defects,
  3. Pediatric cancer-predisposing genetic conditions,
  4. Cancer in children from families in the absence of a clearly defined cancer-predisposing genetic disorder, and
  5. Cancer in children with non-familial chromosomal syndromes.

A workshop focusing on "Birth Defects and Cancer Risk: The Intersection of Genes and Prenatal Exposures" will be the first step in highlighting opportunities and challenges in improving upon and developing new methodologies and resources to study the role of genetics, environmental exposures and gene-environment interaction in etiologies of childhood cancers, and birth defects. For each topic, an expert with diverse perspectives will offer an assessment of the state of the science, main challenges, and most attractive opportunities. Moderators will lead active discussions among the speakers and the participants.

In addition, a major part of the workshop will be a panel discussion by several experts, and a moderator will facilitate interactions among the panelists and the participants. The goal of this multidisciplinary panel discussion will be to clarify and prioritize the major recommendations from the workshop with regard to enhancing scientific knowledge of the nexus between birth defects and cancer with the goal of preventing these conditions.

Deliverables and outcomes include:

  1. White paper describing research gaps.
  2. Workshop report published in a journal.
  3. Solid research project ideas that could be developed into NCI applications (potentially with accompanying Request for Applications (RFA) or Program Announcement (PA)). Such Funding Opportunity Announcements could include mechanisms to link national registries and systems; leverage ongoing and past case-control and other epidemiologic studies, and/or genomic studies; and encourage interdisciplinary collaborations to further progress.
  4. Create opportunities to initiate linkage between birth defects, exposure data (prenatal, preconception, environmental factors) and childhood cancers.
  5. Opportunities to create an infrastructure for linking and pooling data for research purposes.

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Agenda

View Agenda for Day 1 of the Birth Defects and Cancer Workshop
September 10 Topic
8:30 a.m. - 9:00 a.m. Registration
9:00 a.m. - 9:15 a.m. Introductory Remarks
9:15 a.m. - 9:30 a.m. Workshop Overview and Objectives

Somdat Mahabir, Ph.D., M.P.H.
Program Director, Modifiable Risk Factors Branch
Epidemiology and Genomics Research Program
Division of Cancer Control and Population Sciences
National Cancer Institute (NCI)

9:30 a.m. - 10:15 a.m. Epidemiology of birth defects and cancer: State of the evidence, opportunities and challenges (will also cover links with in utero exposures)

Keynote speaker: Andrew Olshan, Ph.D.
Professor and Chair
Department of Epidemiology
Gillings School of Global Public Health,
University of North Carolina, Chapel Hill

10:15 a.m. - 10:30 a.m. Moderator: Jennita Reefhuis, Ph.D.
Centers for Disease Control and Prevention (CDC)
10:30 a.m. - 10:45 a.m. Break
10:45 a.m. - 11:15 a.m. Genomic causes in birth defects-cancer nexus

Speaker: Katherine A. Rauen, M.D., Ph.D.
Associate Professor
Director, NF/Ras Pathway Clinic
Associate Director, Medical Genetics Residency Program
UCSF Helen Diller Family Comprehensive Cancer Center

11:15 a.m. - 11:30 a.m. Moderator: Logan Spector, Ph.D.
University of Minnesota
11:30 a.m. - 12:00 p.m. Developmental pathways linking birth defects to cancer

Speaker: Alexandra L. Joyner, Ph.D.
Courtney Steel Chair in Pediatric Cancer Research
Memorial Sloan-Kettering Cancer Center

12:00 p.m. - 12:15 p.m. Moderator: Lorette Javois, Ph.D.
Eunice Kennedy Schriver National Institute of Child Health and Human Development (NICHD)
12:15 p.m. - 1:00 p.m. Lunch
1:00 p.m. - 1:30 p.m. Experimental insights into the mechanisms linking birth defects to cancer

Speaker: Lucy Anderson, Ph.D., D.A.B.T.
Chief, Cellular Pathogenesis Section (Retired)
Laboratory of Comparative Carcinogenesis, NCI

1:30 p.m. - 1:45 p.m. Moderator: Gary Shaw, Dr.P.H.
Stanford University
1:45 p.m. - 2:15 p.m. Methodological challenges in studying birth defects and cancer

Speaker: W. Dana Flanders, M.D., D.Sc.
Professor, Department of Epidemiology, Biostatistics and Bioinformatics
Rollins School of Public Health, Emory University

2:15 p.m. - 2:30 p.m. Moderator: Somdat Mahabir, Ph.D., M.P.H.
NCI
2:30 p.m. - 2:45 p.m. Break
2:45 p.m. - 3:15 p.m. Opportunities to link databases to study birth defects and subsequent cancer development

Speaker: Martha Linet, M.D., M.P.H.
Chief and Senior Investigator, Radiation Epidemiology Branch
Division of Cancer Epidemiology and Genetics, NCI

3:15 p.m. - 3:30 p.m. Moderator: Andrew Olshan, Ph.D.
University of North Carolina, Chapel Hill
3:30 p.m. - 3:45 p.m. What do we know about the role of birth defects and prenatal exposures as risk factors for childhood cancer and what are the future recommendations for research?

Remarks by Moderator:Gary Shaw, Dr.P.H.
Professor, Pediatrics-Neonatal and Developmental Medicine
Associate Chair, Clinical Research
Stanford University School of Medicine

3:45 p.m. - 4:30 p.m. Remarks by Panelists

Martha Linet, M.D., M.P.H., NCI
Andy Olshan, Ph.D., University of North Carolina, Chapel Hill
Sonja A. Rasmussen, M.D., M.S., CDC
Julie Ross, Ph.D., University of Minnesota
Sharon Savage, M.D., F.A.A.P., NCI
Logan Spector, Ph.D., University of Minnesota

4:30 p.m. - 5:15 p.m. Questions for Panelists
5:15 p.m. - 5:30 p.m. Summary and Follow-up

Somdat Mahabir, Ph.D., M.P.H.
Program Director, Modifiable Risk Factors Branch
Epidemiology and Genomics Research Program
Division of Cancer Control and Population Sciences, NCI

5:30 p.m. Adjourn

View Agenda for Day 2 of the Birth Defects and Cancer Workshop
September 11 Topic
9:00 a.m. - 1:00 p.m. Steering Committee Members, Speakers, Moderators (Closed deliberations)
  • Summary of the workshop - scope of the problem, gaps, future directions
  • Specific recommendations for actions
  • Workshop follow-up
  • Paper

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Steering Committee

  • Somdat Mahabir, National Cancer Institute, NIH
  • Martha Linet, National Cancer Institute, NIH
  • Andrew Olshan, University of North Carolina, Chapel Hill
  • Logan Spector, University of Minnesota
  • Gary Shaw, Stanford University
  • Jennita Reefhuis, Centers for Disease Control (CDC)
  • Lorette Javois, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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Contact

For questions, contact workshop organizer Somdat Mahabir, Ph.D., M.P.H., Program Director, Modifiable Risk Factors Branch, Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, NIH.

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