Pediatric Rhabdomyosarcoma: Epidemiology and Genetic Susceptibility

Abstract

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children, yet little is known about its etiology. Studies that examine either environmental exposures or germline genetic predisposition in RMS have begun to identify factors that contribute to this malignancy. Here, we summarize epidemiological reports of RMS incidence in terms of several factors, including age at diagnosis, biological sex, and geographic location. We then describe findings from association studies, which explore the role of parental exposures, birth and perinatal characteristics, and childhood exposures in RMS. Further, we discuss RMS predisposition syndromes and large-scale sequencing studies that have further identified RMS-associated genes. Finally, we propose future directions of study, which aim to advance our understanding of the origin of RMS and can provide knowledge for novel RMS therapies.

Keywords: cancer predisposition; epidemiology; genetic susceptibility; pediatric cancer.

Figure 1

Age-incidence curve of rhabdomyosarcoma (RMS) in terms of the major histological subtypes: embryonal RMS (ERMS) and alveolar RMS (ARMS). The data represent the incidences from 2000–2017 and was published by the Surveillance, Epidemiology, and End Results (SEER) program.

Figure 2

Incidence of RMS per 1,000,000 children by geographic location. Bar color indicates geographic location by continent. RMS incidence in Africa is presented as two countries per region, which illustrate the minimum and maximum values of the range by region, as reported by Stefan et al. [27].

Figure 3

The Ras signaling pathway and proteins encoded by genes that are implicated in each of the cancer predisposition RASopathies: Costello syndrome, neurofibromatosis type I, and Noonan syndrome.