Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and the U.S. Surveillance Epidemiology and End Results (SEER) registry reports that Hispanic children have the highest incidence of ALL; however, it is unclear if this is due to genetic factors, unique environmental exposures, or both. Previous research has shown that there is an association between CYP1A1 gene variants and ALL. In order to investigate whether there was a specific genetic abnormality that could be statistically associated with a particular ethnic group, collaborative studies between Drs. Tomlinson and Pollock were undertaken to analyze genetic factors in blood samples from 258 children (Caucasian, Hispanic, and African-American) diagnosed with ALL in Central-South Texas. Allele frequencies among the cases and controls in each ethnic group were compared using the Chi-square test.
Increased risk of developing ALL was found in the whole sample group for homozygosity of variant alleles at CYP1A1*2C. Of note, stratified analyses showed not only increased risks in the Hispanic group, but also that Hispanic normal control subjects were significantly more likely to be carriers of variant alleles as compared to Caucasians and African Americans. This study suggests that polymorphisms in CYP1A1 may contribute to the increased risk of ALL in Hispanic children due to both their impact on leukemia susceptibility and the increased prevalence of the at-risk alleles in the Hispanic population.
This is the first investigation that links the prevalence CYP1A1 polymorphisms to the increased susceptibility of ALL in Hispanic children. Additionally, the CYP1A1*2A allele is reported to be associated with increased enzymatic activity. As a consequence, individuals carrying the at-risk alleles are more likely to be at higher risk when exposed to carcinogens. The results of this study provide a novel and specific link between CYP1A1 polymorphisms and ethnic influence on ALL risk that may be related to varying susceptibility across ethnic groups to environmental toxins.