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Abstract 722: Metals in primary teeth and childhood acute lymphoblastic leukemia: A pilot study


 Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, but few environmental risk factors have been confirmed, mostly due to imprecise self-reported questionnaire data. This highlights the need for epidemiological studies to employ novel exposure assessment methods to objectively measure early life exposures. Many metals are considered known or probable human carcinogens, primarily based on studies of adult cancers. We seek to determine the association between pre- and postnatal uptake of metals and ALL risk.
 Methods: Children with and without ALL were recruited from Texas Children’s Hospital. Each participant donated 2-5 primary teeth for analysis. Using laser ablation-inductively coupled plasma-mass spectrometry, we measured 8 metals (arsenic, cadmium, chromium, copper, lead, manganese, magnesium, zinc) and calcium in teeth from 61 children with ALL and 6 without. In teeth, dentin and enamel form at different times, creating visible growth rings, which allowed us to objectively measure metal uptake for every week from up to 20 weeks before birth to 55 weeks after birth. At each timepoint, the ratio of metal to calcium was calculated to normalize the data. For each metal, we calculated the average prenatal uptake (i.e., 20 weeks before birth to birth) and average postnatal uptake (i.e., first week after birth to last available measurement). The average metal uptake in cases were compared to controls. To identify more specific window(s) of susceptibility, we used distributed lag regression, allowing us to incorporate data measured at all timepoints.
 Results: Compared to children without ALL, children with ALL on average had higher prenatal uptake of chromium (0.50 vs 0.43; p=0.07), manganese (1,969 vs 1,888; p=0.20), and lead (0.04 vs 0.02; p=0.03) and lower prenatal uptake of cadmium (0.01 vs 0.02; p=0.0004), copper (0.07 vs 0.10; p=0.19), magnesium (0.24 vs 0.29; p=0.35), and zinc (22 vs 24; p=0.01). Average prenatal uptake of arsenic was similar between cases and controls (0.01 vs 0.01; p=0.13). A similar pattern was observed with postnatal uptake of metals. Using distributed lag regression, prenatal uptake of manganese 10 to 20 weeks before birth was significantly associated (p<0.05) with risk of ALL, but a significantly protective association was observed starting at ~5 weeks after birth. While no other metals had a significant association with ALL, there was suggestive evidence that pre- and postnatal uptake of lead and chromium were positively associated with ALL, while pre- and postnatal uptake of zinc and copper were inversely associated.
 Conclusion: Using a novel exposure method to measure metal uptakes at specific windows of susceptibility in primary teeth samples, our results suggest certain metals may contribute to the etiology of ALL. A larger study is needed to draw more definitive conclusions about early-life uptake of metals and risk of ALL.
 Citation Format: Thanh Hoang, Manish Arora, Christine Austin, Paul C. Curtin, Philip J. Lupo, Michael E. Scheurer. Metals in primary teeth and childhood acute lymphoblastic leukemia: A pilot study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 722.