Abstract 6213: T-cell receptor excision circles (TRECs) at birth and risk of childhood cancers

Abstract Introduction: Acquired immunosuppression is associated with higher risk for infection-related cancers. However, cancer risk among children born with primary immunodeficiency is unknown. Circulating T-cell receptor excision circles (TRECs) are a marker of thymus production of T-cells, which is used to identify severe combined immunodeficiency (SCID) at very low levels during newborn screening. It is unknown whether TREC levels at birth are associated with cancer risk in children. Methods: The California (CA) and Texas (TX) cancer registries identified cancers in children aged 0-5 years born during 2013-2018. Controls were matched to cases by birth year and sex. TREC levels, measured at birth by the state SCID screening programs were linked to cases and controls. Conditional logistic regression was used to assess the association between tertiles (T) of TREC levels and cancer risk. Results: We included 1, 450 cancer cases and 7, 250 controls from TX and 2, 564 cases and 12, 820 controls from CA. Only 13 newborns in CA and 15 in TX had extremely low TREC level at birth. T2 levels of TREC was inversely associated with cancer risk compared to the lowest (T1), for several cancers(Table 1). However, only acute myeloid leukemia showed an inverse association for T2 and T3 in CA (odds ratio [OR] 95%CI: T2, 0.38, 0.22-0.66; T3, 0.47, 0.27-0.82), but this was not replicated in TX. Both T2 and T3 were associated with increased risk of acute lymphoblastic leukemia in TX (T2, 1.45, 1.05-1.99; T3, 1.49, 1.06-2.08) but not in CA. Conclusion: SCID is rare among children with cancer. We did not see consistent associations between TREC levels and cancer risk, either across tertile levels or between CA and TX. This indicates that differences in immune function do not contribute to the etiology of the childhood cancers examined. Alternatively, TREC assays are designed to detect children with the abnormally low TREC levels, and higher TREC levels may not reflect immune function. Citation Format: Jun Tao, Paul S. Albert, Nellie Gottlieb, Eric A. Engels. T-cell receptor excision circles (TRECs) at birth and risk of childhood cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6213.