Abstract

BackgroundThe presence of a congenital anomaly is associated with increased childhood cancer risk, likely due to large effects of Down syndrome and chromosomal anomalies for leukemia. Less is known about associations with presence of non-chromosomal anomalies.MethodsRecords of children diagnosed with cancer at <20 years of age during 1984–2013 in Washington State cancer registries were linked to their birth certificates (N = 4,105). A comparison group of children born in the same years was identified. Congenital anomalies were assessed from birth records and diagnosis codes in linked hospital discharge data. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for cancer, and for specific cancer types in relation to the presence of any anomaly and specific anomalies.ResultsHaving any congenital anomaly was associated with an increased risk of childhood cancer (OR: 1.46, 95% CI 1.28–1.65). Non-chromosomal anomalies were also associated with increased childhood cancer risk overall (OR: 1.35; 95% CI: 1.18–1.54), and with increased risk of several cancer types, including neuroblastoma, renal, hepatoblastoma, soft-tissue sarcoma, and germ cell tumors. Increasing number of non-chromosomal anomalies was associated with a stronger risk of childhood cancer (OR for 3+ anomalies: 3.11, 95% CI: 1.54–6.11). Although central nervous system (CNS) anomalies were associated with CNS tumors (OR: 6.05, 95% CI 2.75–13.27), there was no strong evidence of other non-chromosomal anomalies being specifically associated with cancer occurring in the same organ system or anatomic location.ConclusionsNon-chromosomal anomalies increased risk of several cancer types. Additionally, we found that increasing number of non-chromosomal anomalies was associated with a stronger risk of cancer. Pooling similar data from many regions would increase power to identify specific associations in order to inform molecular studies examining possible common developmental pathways in the etiologies of birth defects and cancer.

Highlights

  • Congenital anomalies are one of the strongest and most consistent risk factors for childhood cancer

  • Having any congenital anomaly was associated with an increased risk of childhood cancer (OR: 1.46, 95% CI 1.28–1.65)

  • Non-chromosomal anomalies were associated with increased childhood cancer risk overall (OR: 1.35; 95% CI: 1.18–1.54), and with increased risk of several cancer types, including neuroblastoma, renal, hepatoblastoma, soft-tissue sarcoma, and germ cell tumors

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Summary

Introduction

Congenital anomalies (i.e., birth defects) are one of the strongest and most consistent risk factors for childhood cancer. Birth defects are generally categorized as chromosomal or nonchromosomal anomalies.[1] The role of chromosomal anomalies on childhood cancer risk has been described. Children with Down syndrome (DS) have a 20-fold increased risk of acute lymphoblastic leukemia (ALL) compared to those without DS.[2, 3] children with chromosome 13q14 deletion syndrome, characterized by dysmorphic facial features, have increased risk of retinoblastoma.[4] Four recent population-based registry linkage studies in the United States (U.S.)[2, 5,6,7] suggest that children with non-chromosomal anomalies may be more likely to develop cancer compared to their unaffected contemporaries. The presence of a congenital anomaly is associated with increased childhood cancer risk, likely due to large effects of Down syndrome and chromosomal anomalies for leukemia. Less is known about associations with presence of non-chromosomal anomalies

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