Erin C Peckham-Gregory1, Kenneth L McClain1, Carl E Allen2, Michael E Scheurer1, Philip J Lupo3. 1. Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX; Texas Children's Cancer and Hematology Centers, Texas Children's Hospital, Houston, TX. 2. Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX; Texas Children's Cancer and Hematology Centers, Texas Children's Hospital, Houston, TX; Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX. 3. Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX; Texas Children's Cancer and Hematology Centers, Texas Children's Hospital, Houston, TX. Electronic address: philip.lupo@bcm.edu.
Abstract
PURPOSE: Potential roles of inherited and environmental risk factors in pathogenesis of Langerhans cell histiocytosis (LCH), a myeloid neoplastic disorder, are undefined. We therefore evaluated the role of parental and perinatal factors on the risk of this childhood cancer. METHODS: Information on LCH cases (n = 162) for the period 1995-2011 was obtained from the Texas Cancer Registry. Birth certificate controls were frequency-matched on year of birth at a ratio of 10:1 for the same period. Variables evaluated included parental age, race/ethnicity, size for gestational age, and birth order. Logistic regression was used to generate an adjusted odds ratio (aOR) and 95% confidence interval (CI) testing the association between each factor and LCH. RESULTS: Few perinatal or parental factors were associated with LCH risk, with the exception of race/ethnicity. Mothers of Hispanic ethnicity were more likely to have children who developed LCH compared to non-Hispanic whites (aOR: 1.51; 95% CI: 1.02-2.25). This risk increased when both parents were Hispanic (aOR: 1.80; 95% CI: 1.13-2.87). Non-Hispanic black mothers were suggested as less likely to give birth to offspring who developed LCH compared to non-Hispanic whites (aOR: 0.50; 95% CI: 0.24-1.02). CONCLUSIONS: LCH is characterized by somatic mutations in MAPK pathway genes in myeloid precursors. Increased risk for LCH in children of Hispanic parents suggests potential impact of inherited factors on LCH pathogenesis.
PURPOSE: Potential roles of inherited and environmental risk factors in pathogenesis of Langerhans cell histiocytosis (LCH), a myeloid neoplastic disorder, are undefined. We therefore evaluated the role of parental and perinatal factors on the risk of this childhood cancer. METHODS: Information on LCH cases (n = 162) for the period 1995-2011 was obtained from the Texas Cancer Registry. Birth certificate controls were frequency-matched on year of birth at a ratio of 10:1 for the same period. Variables evaluated included parental age, race/ethnicity, size for gestational age, and birth order. Logistic regression was used to generate an adjusted odds ratio (aOR) and 95% confidence interval (CI) testing the association between each factor and LCH. RESULTS: Few perinatal or parental factors were associated with LCH risk, with the exception of race/ethnicity. Mothers of Hispanic ethnicity were more likely to have children who developed LCH compared to non-Hispanic whites (aOR: 1.51; 95% CI: 1.02-2.25). This risk increased when both parents were Hispanic (aOR: 1.80; 95% CI: 1.13-2.87). Non-Hispanic black mothers were suggested as less likely to give birth to offspring who developed LCH compared to non-Hispanic whites (aOR: 0.50; 95% CI: 0.24-1.02). CONCLUSIONS: LCH is characterized by somatic mutations in MAPK pathway genes in myeloid precursors. Increased risk for LCH in children of Hispanic parents suggests potential impact of inherited factors on LCH pathogenesis.
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