Variation at 7p12.2 and 10q21.2 influences childhood acute lymphoblastic leukemia risk in the Thai population and may contribute to racial differences in leukemia incidence

Abstract

Recent genome-wide association (GWA) studies of childhood acute lymphoblastic leukemia (ALL) have identified 7p12.2, 9p21.3, 10q21.2, and 14q11.2 SNPs that confer modest risks of ALL. These studies have been conducted in European populations, and it is unclear whether these observations generalize to other populations with a lower incidence of ALL. To explore the impact of these variants on ALL risk in the Thai population, we genotyped 190 cases of ALL and 182 controls for SNPs rs4132601 (7p12.2), rs3731217 (9p21.3), rs7089424 and rs10821938 (10q21.2), and rs2239633 (14q11.2). Consistent with findings in European populations, rs4132601 genotype was significantly associated with risk of ALL (odds ratio [OR] = 1.57, 95% confidence interval [CI]: 1.01–2.44; p = 0.04), and rs10821938 genotype was significantly associated with B-cell precursor ALL (OR = 0.73, 95% CI: 0.55–0.97; p = 0.03). There were, however, differences in allele frequencies in SNPs observed between Thai and Caucasian populations (e.g. IKZF1, rs4132601; risk allele frequency [RAF] ratio of 0.36 for Thai/Caucasian). These differences, combined with differences in linkage disequilibrium structure between populations or differences in effect size between populations, may contribute to racial differences in ALL incidence.

Keywords:

• Polymorphism
• risk
• acute lymphoblastic leukemia

Acknowledgements

We are grateful to all the patients and individuals for their participation, and finally we would also like to thank the clinicians, other hospital staff, and study staff who contributed to the blood sample and data collection for this study.

Declaration of interest: Leukemia Lymphoma Research provided principal funding for the study. Support from Cancer Research UK (C1298/A8362 supported by the Bobby Moore Fund) is also acknowledged.