Genetic Overlap Between Anomalies and Cancer in Kids in the Children's Oncology Group: The COG GOBACK Study

Summary

One of the strongest risk factors for cancer in children and adolescents is being born with a congenital anomaly. In fact, data from registry linkage studies imply that 10-15% of childhood cancer risk could be attributable to having a congenital anomaly. As an estimated 10 million children worldwide are born with a congenital anomaly per year, the public health implications of identifying why some of these children develop cancer are thus substantial. While these studies have been informative, registry data alone offers no possibility of molecular or sequencing studies to identify the specific genetic basis underlying the co-occurrence of anomalies and cancer susceptibility. Therefore, the investigators developed the first phase of the Genetic Overlap Between Anomalies and Cancer in Kids (GOBACK) Study to address these limitations. Using data from birth defects and cancer registries from four states, the investigators identified numerous novel specific anomaly-cancer associations. In the GOBACK Study the investigators identified an increase in cancer risk among children with any chromosomal abnormality and any non-chromosomal birth defect. Additionally, children with congenital anomalies developed a variety of cancers, therefore the investigators propose to evaluate a range of cancers among children with congenital anomalies. By pooling registry data across four states in the GOBACK Study, the investigators found that children with non-chromosomal birth defects have a significantly elevated risk of several childhood cancers. Notably several of these congenital anomalies are not characteristic of known cancer predisposition syndromes. Therefore, our preliminary studies lay the framework for this application. The objectives of the current study are to (1) interrogate the genomes of children with co-occurring non-chromosomal congenital anomalies and cancer enrolled in Project:EveryChild to identify genetic features associated with these combined phenotypes, and (2) verify congenital anomalies and determine the phenotypic spectrum among children with cancer enrolled in Project:EveryChild with self-reported congenital anomalies ("deep phenotyping"). For this study the investigators will utilize Project:EveryChild to identify, contact, and enroll case-parent trios for children with co-occurring non-chromosomal congenital anomalies and cancers. From each enrolled family the investigators e will collect DNA from the affected case and one or both biological parents to comprise each case-parent trio. The investigators will include siblings if available. The investigators will also characterize case-parent trios based on demographic and clinical characteristics utilizing information collected via self-administered questionnaires and medical records. Ultimately the findings from this study could lead to 1) determining the potential genetic mechanisms that underlie these co-occurring conditions; 2) improving cancer risk-management strategies among children with birth defects; and 3) identifying the role congenital anomalies play in outcomes and survivorship among children diagnosed with cancer.

Conditions

• Congenital Anomaly
• Pediatric Cancer

Interventions

OTHER

Whole Genome Sequencing

Saliva collection and request for banked blood and tumor samples for sequencing

OTHER

Questionnaire Administration

Study questionnaire will include modules that collect information on maternal reproductive history, exposure to known teratogens, medical history, and previous genetic testing.

OTHER

Biospecimen collection

Saliva collection and request for banked blood and tumor samples for sequencing and biomarker analysis

OTHER

Laboratory Biomarker Analysis

Saliva collection and request for banked blood and tumor samples for biomarker analysis

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• Children's Oncology Group

  lead NETWORK

Eligibility

Min Age

0 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-09-10

Primary Completion

2026-09-30

Completion

2027-09-30

Countries

• United States

Study Locations