Role of Fetal Growth in Pediatric Rhabdomyosarcoma
Pediatric RMS is the commonest soft tissue sarcoma in children. Despite improvements in therapy, a third or more die or experience recurrence within five years. Due largely to its rarity, the etiology of pediatric RMS remains poorly understood. Mounting evidence supports a key role of fetal growth characteristics in disease risk.
Using an innovative statewide database linkage between the cancer registry, birth registry and the repository of neonatal dried bloodspot specimens collected by the California Department of Public Health, we propose to conduct a study of the role of both fetal growth characteristics and genes encoding fetal growth in pediatric RMS. We will first examine the role of fetal growth characteristics (e.g., birth weight, size for gestational age) using data from 700 cases and 2800 age-, gender-, and race/ethnicity-matched controls. Next, we will apply high-density genotyping panels to dried bloodspot DNA available for 275 of these cases and compare genetic variation between these cases and 4,000 California children free of cancer.
We will adopt a staged analysis approach that focuses first on genes involved in fetal growth regulation, and later expand to a genome-wide analysis to identify novel risk-associated gene regions. We will follow up with replication of the identified disease-associated loci in an independent set of dried bloodspot specimens from 275 RMS cases and 550 controls. Our goal is to conduct a robust appraisal of the role of fetal growth in pediatric RMS, to identify etiologically relevant loci that may be targets for future prevention or therapy.