Family history of cancer and childhood rhabdomyosarcoma: a report from the Children's Oncology Group and the Utah Population Database.

Philip J Lupo,Beatrice Melin,Karen Curtin,Logan G Spector,Douglas S Hawkins,Simone Hettmer,Sharon E Plon,Joshua D Schiffman,David Malkin,Karin Papworth,Heather E Danysh,Stephen X Skapek,Erik B Erhardt,Seymour Grufferman

doi:10.1002/cam4.448

Abstract

Relatively little is known about the epidemiology and factors underlying susceptibility to childhood rhabdomyosarcoma (RMS). To better characterize genetic susceptibility to childhood RMS, we evaluated the role of family history of cancer using data from the largest case–control study of RMS and the Utah Population Database (UPDB). RMS cases (n = 322) were obtained from the Children's Oncology Group (COG). Population-based controls (n = 322) were pair-matched to cases on race, sex, and age. Conditional logistic regression was used to evaluate the association between family history of cancer and childhood RMS. The results were validated using the UPDB, from which 130 RMS cases were identified and matched to controls (n = 1300) on sex and year of birth. The results were combined to generate summary odds ratios (ORs) and 95% confidence intervals (CI). Having a first-degree relative with a cancer history was more common in RMS cases than controls (ORs = 1.39, 95% CI: 0.97–1.98). Notably, this association was stronger among those with embryonal RMS (ORs = 2.44, 95% CI: 1.54–3.86). Moreover, having a first-degree relative who was younger at diagnosis of cancer (<30 years) was associated with a greater risk of RMS (ORs = 2.37, 95% CI: 1.34–4.18). In the largest analysis of its kind, we found that most children diagnosed with RMS did not have a family history of cancer. However, our results indicate an increased risk of RMS (particularly embryonal RMS) in children who have a first-degree relative with cancer, and among those whose relatives were diagnosed with cancer at <30 years of age.

Highlights

Rhabdomyosarcoma (RMS) is a malignant tumor of skeletal muscle
While not statistically significant, having any first-degree relative with cancer was positively associated with childhood RMS (Table 2) (ORs = 1.39, 95% confidence intervals (CI): 0.97–1.98)
In the largest analysis of its kind to date, we found that most RMS cases did not have a first-degree relative with a history of cancer

Summary

Introduction

Rhabdomyosarcoma (RMS) is a malignant tumor of skeletal muscle. While RMS is the most common soft tissue sarcoma in children [1], the annual incidence is only 4.6 per million in people younger than 20 years of age [2]. Within Li-Fraumeni syndrome (LFS) families that carry germline TP53 mutations, RMS is one of the most common childhood malignancies [9, 10]. In one report from the fourth trial of the Intergroup Rhabdomyosarcoma Study Group (IRSIV), the prevalence of neurofibromatosis type 1 was ~20 times greater in children with RMS compared to the general population (0.5% vs 0.02–0.03%) [11]. In spite of these associations, much work remains in characterizing the role of genetic susceptibility in the etiology of childhood RMS

Methods

Results

Conclusion