Abstract
Although little is known about etiology of childhood rhabdomyosarcoma (RMS), early life factors are suspected in the etiology. We explored this hypothesis using linked data from the California Cancer Registry and the California birth rolls. Incident cases were 359 children <6-year-old (218 embryonal, 81 alveolar, 60 others) diagnosed in 1988–2008. Controls (205, 173), frequency matched on birth year (1986–2007), were randomly selected from the birth rolls. We examined association of birth characteristics such as birth weight, size for gestational age, and timing of prenatal care with all-type RMS, embryonal, and alveolar subtypes. Crude and adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression. In contrast to a previous study, we observed statistically non-significant association for embryonal subtype among high birth weight (4000–5250 g) children for term births [OR (95% CI): 1.28 (0.85, 1.92)] and all births adjusted for gestational age [OR (95% CI): 1.21 (0.81, 1.81)]. On the other hand, statistically significant 1.7-fold increased risk of alveolar subtype (95% CI: 1.02, 2.87) was observed among children with late or no prenatal care and a 1.3-fold increased risk of all RMS subtypes among children of fathers ≥35 years old at child birth (95% CI: 1.00, 1.75), independent of all covariates. Our finding of positive association on male sex for all RMS types is consistent with previous studies. While we did not find a convincingly positive association between high birth weight and RMS, our findings on prenatal care supports the hypothesis that prenatal environment modifies risk for childhood RMS.
Highlights
Rhabdomyosarcoma (RMS) is the most common type of softtissue sarcoma among 0- to 19-year-olds, with the incidence rate highest among children of ages 0–4 [1]
In terms of other perinatal characteristics, we found statistically significant increased risk for all-type RMS and embryonal RMS among male compared to female children, and for alveolar RMS among those with late initiated or no prenatal care [odds ratios (ORs): 1.52 (1.23, 1.89), 1.60 (1.22, 2.11), and 1.71 (1.02, 2.87) respectively] after adjusting for all covariates
Positive associations were suggested for birth weight with all of the measures we employed and embryonal RMS
Summary
Rhabdomyosarcoma (RMS) is the most common type of softtissue sarcoma among 0- to 19-year-olds, with the incidence rate highest among children of ages 0–4 [1]. Embryonal and alveolar RMS are the two main histological subtypes, accounting for over 90 percent of cases in children under the age of five [2]. RMS is often characterized by overexpression of the gene encoding insulin-like growth factor 2 (IGF2). This can result from either loss of heterozygosity (LOH, observed in both subtypes) due to the loss of the maternal allele and duplication of paternal allele, or loss of imprinting (LOI) via hypomethylation of the maternal IGF2 allele (observed in embryonal RMS [4,5,6,7]). Germline mutations of the TP53 gene, implicated in regulation of IGF2 expression, are often associated with early onset of RMS [9,10,11]
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