The genetic risk of acute lymphoblastic leukemia and its implications for children of Latin American origin

Abstract

Acute lymphoblastic leukemia (ALL) is the most common cancer in children, and disproportionately affects children of Hispanic/Latino ethnicity in the United States, who have the highest incidence of disease compared with other racial/ethnic groups. Incidence of childhood ALL is similarly high in several Latin American countries, notably in Mexico, and of concern is the rising incidence of childhood ALL in some Hispanic/Latino populations that may further widen this disparity. Prior studies have implicated common germline genetic variants in the increased risk of ALL among Hispanic/Latino children. In this review, we describe the known disparities in ALL incidence as well as patient outcomes that disproportionately affect Hispanic/Latino children across the Americas, and we focus on the role of genetic variation as well as Indigenous American ancestry in the etiology of these disparities. Finally, we discuss future avenues of research to further our understanding of the causes of the disparities in ALL incidence and outcomes in children of Latin American origin, which will be required for future precision prevention efforts.

Keywords: ALL; Hispanic/Latino; Latin America; childhood acute lymphoblastic leukemia; disparities; genetic epidemiology; genetics; single nucleotide polymorphisms.

Figure 1

5-year age-adjusted incidence rates of childhood acute lymphoblastic leukemia across population groups in SEER, 2016-2020. Incidence rates are per 100,000 including both sexes and individuals < 20 years of age, and are age-adjusted to the 2000 US standard population. Bars represent 95% confidence intervals. Incidence data for Hispanics and non-Hispanics are based on the NAACCR Hispanic Latino Identification Algorithm. Rates for Non-Hispanic American Indian/Alaska Native include cases that are in a Purchased/Referred Care Delivery Area. Figure generated from data downloaded from the SEER*Explorer website (reference 16).

Figure 2

Risk allele frequency of selected SNPs associated with childhood acute lymphoblastic leukemia risk. Single nucleotide polymorphisms (SNPs, n=28, Table 1 ) are grouped by nearest genes in each panel. Left: Absolute difference in risk allele frequency between Latinos/Admixed Americans and non-Finnish Europeans in gnomAD v3.1. Right: Percentage difference in SNP risk allele frequencies between Latinos/Admixed Americans and non-Finnish Europeans. Percentage change equation: {[(Risk allele frequency of Latinos/Admixed Americans)/(Risk allele frequency of non-Finnish Europeans)] - 1} x 100. Horizontal bars are colored by the direction of percentage difference.