Data from Genetic Polymorphisms in Adaptive Immunity Genes and Childhood Acute Lymphoblastic Leukemia

Abstract

<div>Abstract<p><b>Background:</b> Childhood acute lymphoblastic leukemia (ALL) has been hypothesized to have an infection- and immune-related etiology. The lack of immune priming in early childhood may result in abnormal immune responses to infections later in life and increase ALL risk.</p><p><b>Methods:</b> The current analyses examined the association between childhood ALL and 208 single-nucleotide polymorphisms (SNP) of 29 adaptive immune function genes among 377 ALL cases and 448 healthy controls. Single SNPs were analyzed with a log-additive approach using logistic regression models adjusted for sex, age, Hispanic ethnicity, and race. Sliding window haplotype analyses were done with haplotypes consisting of 2 to 6 SNPs.</p><p><b>Results:</b> Of the 208 SNPs, only rs583911 of <i>IL12A</i>, which encodes a critical modulator of T-cell development, remained significant after accounting for multiple testing (odds ratio for each copy of the variant G allele, 1.52; 95% confidence interval, 1.25-1.85; <i>P</i> = 2.9 × 10<sup>−5</sup>). This increased risk was stronger among firstborn children of all ethnicities and among non-Hispanic children with less day care attendance, consistent with the hypothesis about the role of early immune modulation in the development of childhood ALL. Haplotype analyses identified additional regions of <i>CD28, FCGR2, GATA3, IL2RA, STAT4</i>, and <i>STAT6</i> associated with childhood ALL.</p><p><b>Conclusion:</b> Polymorphisms of genes on the adaptive immunity pathway are associated with childhood ALL risk.</p><p><b>Impact:</b> Results of this study support an immune-related etiology of childhood ALL. Further confirmation is required to detect functional variants in the significant genomic regions identified in this study, in particular for <i>IL12A</i>. Cancer Epidemiol Biomarkers Prev; 19(9); 2152–63. ©2010 AACR.</p></div>