Abstract 6370: Evaluating the risk of carcinomas among children with congenital anomalies: A population-based study of 21 million births

Abstract Background: Carcinomas in childhood are rare, limiting our understanding of their epidemiology. While congenital anomalies are one of the strongest risk factors for childhood cancer overall, their association with carcinomas is understudied. We evaluated the associations between chromosomal and non-chromosomal congenital anomalies and risk of carcinoma through age 18 years. Methods: We leveraged the Genetic Overlap Between Anomalies and Cancer in Kids (GOBACK) Cohort, which includes linked data from population-based birth defects and cancer registries for 21 million births between 1990-2018 in nine U.S. states. We used Cox regression to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the hazard of carcinomas among children with major congenital anomalies relative to children without these conditions, adjusting for sex, state of birth, and maternal age. We performed sensitivity analyses excluding cases diagnosed with carcinomas during the first 2 years of life to assess the potential impact of incidental discovery of anomalies during cancer diagnosis or treatment on our findings. Results: Our study population numbered 21,829,628 children, including 635,632 with major anomalies and 879 with carcinomas (incidence rate: 4.2 per million person-years). Mean follow-up time was 9.6 years. The most common diagnoses were thyroid (N=600 cases) and hepatocellular carcinoma (HCC; N=68 cases). Prevalence of major anomalies was 4.0% in children with carcinomas and 2.9% in children without carcinomas. The hazard of carcinomas was increased for both children with chromosomal or genetic syndromes (HR 5.3, CI 2.6-10.6; N=8) and children with non-syndromic anomalies (HR 1.6, CI 1.2-2.4; N=31). When we evaluated carcinomas by type, we observed associations between 1) chromosomal or genetic syndromes and renal cell carcinoma (HR 57.8, CI 20.7-161.3; N<5), 2) non-syndromic congenital anomalies and HCC (HR 3.8, CI 1.6-8.8; N=6), and to a lesser degree, 3) non-syndromic congenital anomalies and thyroid carcinoma (HR 1.4, CI 0.9-2.2; N=17). Notably, sensitivity analyses suggested associations were not attributable to incidental discovery of anomalies during cancer diagnosis or treatment. Discussion: In this comprehensive assessment of congenital anomalies and carcinomas in children, we report novel associations. The observed associations between congenital anomalies and carcinoma could be due to factors including: 1) common genetic pathways; 2) in utero exposures that lead to both conditions; or 3) postnatal exposures among children with congenital anomalies. Ultimately, our findings could yield new insights into the etiologies of carcinomas in childhood and inform clinical surveillance practices for children with congenital anomalies. Citation Format: Jeremy M. Schraw, Tania A. Desrosiers, Tiffany M. Chambers, Michael E. Scheurer, Charles J. Shumate, Wendy N. Nembhard, Mahsa M. Yazdy, Eirini Nestoridi, Amanda E. Janitz, Jean Paul Tanner, Russell S. Kirby, Jason L. Salemi, Chad D. Huff, Sharon E. Plon, Philip J. Lupo. Evaluating the risk of carcinomas among children with congenital anomalies: A population-based study of 21 million births [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6370.