Circulating T-Cell Receptor Excision Circles at Birth and Risk of Childhood Cancers.
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BACKGROUND: T-cell receptor excision circles (TRECs) are measured in newborn screening programs in the United States to identify severe combined immunodeficiency (SCID). We hypothesized that relatively low TREC levels at birth, even within the normal range, could indicate compromised immunity and higher susceptibility to childhood cancers. METHODS: We conducted a case-control study using linked data from the newborn screening programs and cancer registries in California and Texas to examine the association between TREC levels and risk of childhood cancer. The study included 2196 cancer cases and 10,980 controls from California and 1186 cancer cases and 5890 controls from Texas. RESULTS: In California, acute myeloid leukemia cases had significantly lower TREC levels compared with their matched controls (p = 0.0051), while in Texas, acute lymphocytic leukemia cases had significantly higher TREC levels compared with their matched controls (p = 0.0034). However, each association was not replicated in the other state, and other cancer types did not show significant differences in TREC levels between cases and controls. CONCLUSIONS: We did not observe consistent associations between TREC levels at birth and childhood cancer risk. A possible explanation for the lack of more clear-cut differences in TREC levels between cases and matched controls might be the complex etiology of childhood cancers. The results underscore the need for longitudinal studies that incorporate additional immune biomarkers to understand the immunologic basis of childhood cancer development.