Polymorphisms in CYP1A1 and Ethnic-Specific Susceptibility to Acute Lymphoblastic Leukemia in Children

Abstract

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. 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 reports have shown an association between CYP1A1 variants and ALL.Methods: To explore the contribution of CYP1A1 polymorphisms to ALL susceptibility in different ethnic groups, we conducted a case-control analysis in Caucasian, Hispanic, and African-American children.Results: Increased risk of developing ALL was found in the whole sample group for homozygosity of variant alleles at CYP1A1*2C (OR 2.51, 95% CI 1.18-5.33, P ¼ 0.016) and CYP1A1*2B (OR 3.24, 95% CI 1.43-7.34, P ¼ 0.005). Stratified analyses showed increased risks in the Hispanic group (CYP1A1*2A, OR 2.70, 95% CI 1.27-5.74, P ¼ 0.010; CYP1A1*2C, OR 2.47, 95% CI 1.13-5.38, P ¼ 0.023; and CYP1A1*2B, OR 3.28, 95% CI 1.40-7.69, P ¼ 0.006) but not for the other ethnic groups. Hispanic control subjects were significantly more likely to be carriers of variant alleles as compared to Caucasians (P < 0.0001) and African Americans (P ¼ 0.005).Conclusions: Our 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.Impact: Our study provides a novel and specific link between CYP1A1 polymorphisms and ethnic influence on ALL risk that may help explain varying susceptibilities across groups to environmental toxins. Cancer Epidemiol Biomarkers Prev; 20(7); 1537-42. Ó2011 AACR.

Genetic pattern of CYP1A1*2A (T>C) gene in patients with colorectal cancer in South Jakarta – Indonesia

“…Two common polymorphisms in the CYP1A1 gene are a T6235C change within the 3' noncoding region of the gene (*2A, also known as the MspI restriction) and an A4889G change in the hems-binding domain of exon 7 (*2C). This polymorphism of the gene has been examined to cancer susceptibility [4,5,15].…”

“…The involvement of this enzyme activity in the activation or de-activation shows the individual's susceptibility to cancer. The CYP1A1 polymorphism especially CYP1A1* 2A (T>C) will produce a cutting site for MspI enzyme; it has been linked to individual sensitivity to colon cancer [1][2][3][4][5].…”

Current evidence for an inherited genetic basis of childhood acute lymphoblastic leukemia

“…A second well-characterized variant in this gene, A4889G (rs1048943) evaluated by a fewer number of studies showed an elevated, but non-significant, risk estimate (homozygous: OR = 1.96, 95 % CI 0.92-4.19) in a metaanalysis of three studies [12]. A subsequent study conducted in a multi-ethnic US population of 258 B-lineage ALL cases and 646 matched controls reported a strong increased risk associated with A4889G observed predominantly in Hispanics (dominant: OR = 2.47, 95 % CI 1.13-5.38) [46]. Elevated risk estimates were reported in recent studies conducted in Brazil [47] and a multi-ethnic California population [16], but not in a Korean study [48].…”

Association of serum aryl hydrocarbon receptor activity and RBC omega-3 polyunsaturated fatty acids with flow-mediated dilation in healthy, young Hispanic cigarette smokers

“…These CYPs can generate reactive oxygen species directly by the inefficient coupling of NADPH consumption to substrate oxidation (Kopf and Walker, 2010; Morel et al, 1999; Schlezinger et al, 2006; Zangar et al, 2004) and indirectly by the metabolic activation of PAHs to highly reactive diol-epoxides and dihydrodiols (Bolton et al, 2000; Shimada, 2006). Furthermore, Hispanics commonly carry the CYP1A1*2A polymorphism (Swinney et al, 2011), which results in higher levels of CYP1A1 activity, and this increased CYP1A1 activity may put them at higher risk of cigarette smoke-induced oxidative stress. Thus, the degree to which the AHR is activated and the presence of the CYP1A1*2A polymorphism could be potential predictors of endothelial dysfunction in cigarette smokers.…”