An Evaluation of Parental and Perinatal Characteristics and Risk of Langerhans Cell Histiocytosis in Texas Identifies Risk Disparities By Racial/Ethnic Group

Abstract Introduction: Langerhans cell histiocytosis (LCH) is a myeloid neoplasia with a median diagnosis age of 30 months. As with many pediatric cancers, few well-established risk factors for LCH exist. Maternal and neonatal infections and lack of childhood vaccinations are suspected to increase risk, and LCH incidence has been suggested to differ by racial/ethnic group in United States-based assessments. In studies of other pediatric hematologic malignancies, parental and perinatal characteristics have been successfully evaluated to determine the impact of inborn variation on disease risk. We have reviewed registry data to determine if parental and perinatal characteristics influence LCH development. Methods: We performed a case-control study to investigate the association between parental and perinatal characteristics and pediatric LCH. Information on Texas-born LCH cases (n = 162) for the period 1995-2011 was obtained from the United States (U.S.) Texas Cancer Registry. Birth certificate controls were randomly selected at a ratio of 10:1 for the same period matched on birth year. First, we generated odds ratios (OR) and 95% confidence intervals (CI) to estimate the association between each characteristic and LCH, adjusting for only the matching variable: year of birth. We then calculated an adjusted OR (aOR) including other independent variables if they were: a) differentially distributed between cases and controls at P Results: Our findings indicate specific characteristics influence LCH risk. LCH cases in our study population were predominantly male (56.2%), whereas controls were distributed evenly with respect to sex. Over 40% of cases had two Hispanic parents (42.6%), while only a quarter of cases had two NHW parents (25.9%). Non-Hispanic Black mothers were suggested as less likely to give birth to offspring who developed LCH compared to non-Hispanic White (NHW) mothers (aOR: 0.50; 95% CI: 0.24-1.02). Hispanic mothers were at increased risk of giving birth to offspring who developed LCH compared to NHW mothers (aOR: 1.51; 95% CI: 1.02-2.25). Children born of two Hispanic parents were at a significantly increased risk of developing LCH compared to children born of two non-Hispanic White parents (aOR: 1.76; 95% CI: 1.10-2.80). Children with one non-Hispanic White parent and one non-Hispanic Asian parent were also at increased risk of developing LCH (aOR: 3.68; 95% CI: 1.10-12.33). Mothers who were born in Mexico compared to the U.S. were marginally suggested as less likely to give birth to offspring who developed LCH after adjusting for maternal race/ethnicity (aOR: 0.69; 95% CI: 0.43-1.11). Further, mothers who resided in 1 of 14 Texas counties along the U.S.-Mexico border at time of infant birth were suggested as less likely to give birth to offspring who developed LCH (aOR: 0.56; 95% CI: 0.31-1.03). Conclusion: In this population-based evaluation, maternal and parental race/ethnicity were strongly associated with LCH risk. Furthermore, mothers who resided along the U.S.-Mexico border at time of infant birth may be less likely to give birth to offspring who develop LCH. While no perinatal characteristics were identified that strongly influenced LCH risk, females were marginally suggested as less likely to develop LCH which aligns with previous studies. These findings suggest specific subgroups that may be more susceptible to pediatric LCH, and highlight novel risk factors that warrant assessment in future studies. Disclosures No relevant conflicts of interest to declare.