Abstract A032: Disparities in molecular subtypes of acute lymphoblastic leukemia incidence by age, race/ethnicity, and sex in the United States

Abstract Acute lymphoblastic leukemia (ALL) is the most common cancer in children and a heterogeneous disease comprising several molecular subtypes. The increased risks of ALL in individuals assigned male at birth and in those of Hispanic/Latino ethnicity compared to non-Hispanic White individuals are well known. Less well-established are potential differences in the prevalence of specific molecular subtypes of ALL by sex or racial/ethnic groups. Here, we provide updates on incidence patterns for lymphoid leukemias reported by cancer registries across the United States, leveraging recent data on molecular subtypes of ALL. We obtained data from the North American Association of Central Cancer Registry (NAACCR) for United States-specific incidence cases from 2000 through 2020. Diagnoses and leukemia subtype reporting, limited to ALL only, was based on the International Classification of Diseases for Oncology, Third Edition (ICD-O-3). Age-adjusted (2000 US Standard) incidence rates (AAIR) were calculated using SEER*Stat (version 8.4.3). Incidence rate ratios (IRR) were calculated to assess patterns in leukemia incidence by sex and by race/ethnicity across three age groups: 0- 14 (children), 15-39 (adolescents and young adults, AYA) and 40+ (older adults) years. Information on selected molecular subtypes of ALL was available for cases diagnoses 2010 onwards, from ICD-0-3 histology codes that were determined by genetics and/or immunophenotyping. Overall and in each age group compared to non-Hispanic Whites (NHWs), Blacks/African- Americans (B/AAs) had significantly lower AAIRs for ALL whereas Hispanic/Latinos (H/Ls) had significantly higher AAIRs, in particular for B-cell ALL. Analysis by molecular subtypes revealed that overall, H/Ls were at higher risk for BCR::ABL1 translocation than NHWs, with the greatest difference seen in AYAs in which H/Ls had a 2.5-fold (95% CI=2.08-3.00) higher risk of BCR::ABL1. In children, H/Ls had significantly higher incidences of several ALL subtypes compared with NHWs, including BCR::ABL1 (IRR=1.5; 95% CI=1.13-1.98) and TCF3::PBX1 (IRR=2.0; 95% CI=1.43-2.79) but also ETV6::RUNX1 and high hyperdiploidy (both IRR=1.27; 95% CI=1.12-1.43). Males were at significantly higher risk than females for ALL and its subtypes across all ages combined and stratified age categories. In particular, males had a 2.5- fold increased risk of precursor T-cell lymphoblastic leukemia compared to females (IRR=2.5; 95% CI=2.28-2.73) in all ages combined, and a 3.0-fold increased risk in both AYAs (95% CI=2.59-3.46) and older adults (95% CI=2.54-3.54). Among molecular subtypes, the highest IRR was observed for BCR::ABL1 in AYAs wherein males were at 50% increased risk (IRR=1.5; 95% CI=1.27-1.76). In addition to confirming the previously reported disparities in ALL incidence by race/ethnicity and by sex, we report an increased incidence of particular molecular subtypes of ALL in Hispanics/Latinos and in males. Studies to investigate potential genetic and environmental risk factors underlying these disparities are warranted. Citation Format: Anmol A. Pardeshi, Juanita Elizabeth Quino, Nicholas Acuna, Talar Habeshian, Raymond Hughley, Isabella Ortiz, Michelle Tran, Ying Yan, Cindy Zamora, Joseph l. Wiemels, Kai-Ya Tsai, Lihua Liu, Adam J de Smith. Disparities in molecular subtypes of acute lymphoblastic leukemia incidence by age, race/ethnicity, and sex in the United States [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A032.