Childhood Leukemia in Mexico: Risk Genes, System Gaps

Acute lymphoblastic leukemia (ALL) presents a difficult challenge in terms of diagnosis and treatment, due to limitations in access to healthcare. This form of cancer accounts for 50% of childhood cancer cases in Mexico, as reported by the National Public Health Institute (INSP). While certain GATA3 gene variants significantly increase the risk and aggressiveness of acute lymphoblastic leukemia (ALL) among Mexican children, fewer than 20% of patients have access to advanced diagnostics, and five-year survival rates vary drastically by state, according to the institute.

About 2,000 children die of cancer annually in Mexico alone, reports UNAM. In the population under 20 years of age, leukemia is the cancer type associated with the highest number of deaths, states INSP. Between 1998 and 2018, there was an increase in the proportion of deaths caused by ALL in individuals under 20 years, from 0.3% of total deaths in 1990 to 1.0% in 2000 and 1.3% in 2016. This increase may reflect improvements in diagnostic capacity, as in high-income countries survival has improved significantly, from under 10% in the 1960s to over 80% disease-free survival today. Chile and Argentina have made significant advances, reaching five-year survival rates of 71.6% and 72.1%, respectively. In contrast, five-year overall survival estimates in Mexico range between 40% and 60%.

However, there is considerable variation in pediatric cancer survival across Mexican states, likely due to disparities in healthcare infrastructure and access to services, reports INSP. For example, five-year overall survival under Mexico’s former public health insurance program, Seguro Popular, varied significantly by state, from over 70% in some regions to below 50% in others.

According to the Global Burden of Disease (GBD) study, each child who dies from cancer loses, on average, 70 productive years of life. In Mexico, leukemia accounts for 1.24% of the years lived with disability (YLD) among children aged 5 to 14.

The Challenge of Pre-B Acute Lymphoblastic Leukemia in Mexican Children

Precursor B-cell acute lymphoblastic leukemia (Pre-B-ALL) is an aggressive and the most prevalent type of childhood cancer, representing approximately 25% of all pediatric cancer cases in the United States, with the highest incidence observed in children between the ages of 1 and 4, reports  The National Care Institute.  

According to Frontiers in Oncology, childhood Pre-B-ALL in Mexico is influenced by both genetic and environmental factors. The report highlights a strong association between specific genetic variants in the GATA3 gene and disease susceptibility, with these variants being more common in the Mexican population. These variants are also linked to being overweight, a known risk factor among Mexican children.

Specific variants of the GATA3 gene, particularly rs3824662 and rs3781093, are more common in the Mexican population and have been linked to a higher risk of CRLF2-ALL, an aggressive subtype of childhood acute lymphoblastic leukemia. This genetic change has a notable impact on the risk of developing high-risk leukemia, especially among Hispanic populations, including Mexican children.

Research indicates that these genetic variants boost GATA3 activity, which in turn increases the expression of the CRLF2 gene, a frequent alteration in these aggressive cases of ALL. The presence of these variants is strongly associated with Ph-like ALL, a subtype that is particularly difficult to treat and associated with a poorer prognosis. CRLF2 gene alterations are notably more prevalent in Hispanic and Mexican children, further reinforcing the genetic link to disease severity.

Although the exact prevalence of these genetic risk factors in the broader Mexican population is still under investigation, the existing evidence points to a strong genetic component in the region’s ALL cases, suggesting that genetics plays a significant role in the disease’s higher incidence and severity among Mexican children.

One of the main challenges is timely diagnosis. Pediatric ALL often presents with non-specific symptoms such as fever, anemia, malaise, or bleeding, many of which are also common in infections. Non-leukemic cancers often present with identifiable masses, which may be more easily recognized as malignant. As a result, underdiagnosis may be more prevalent in leukemias than in solid tumors.

Underreporting not only affects treatment response but also hampers resource allocation for prevention, control, and disease monitoring, reports MBN. In Mexico, fewer than 20% of patients have access to such tests, states INSP.