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Cancer. 2016 Dec 1;122(23):3697-3704. doi: 10.1002/cncr.30241. Epub 2016 Aug 16.

Family-based exome-wide assessment of maternal genetic effects on susceptibility to childhood B-cell acute lymphoblastic leukemia in hispanics.

Author information

1
Austin Regional Campus, University of Texas School of Public Health, Austin, Texas.
2
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee.
3
Hematologic Malignancies Program, Comprehensive Cancer Center, St. Jude Children's Research Hospital, Memphis, Tennessee.
4
Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
5
Department of Pediatrics, University of Illinois College of Medicine at Peoria, Peoria, Illinois.
6
National Pediatric Oncology Unit, Guatemala City, Guatemala.
7
School of Medicine, Francisco Marroquin University, Guatemala City, Guatemala.

Abstract

BACKGROUND:

Children of Hispanic ancestry have a higher incidence of acute lymphoblastic leukemia (ALL) compared with other ethnic groups, but to the authors' knowledge, the genetic basis for these racial disparities remain incompletely understood. Genome-wide association studies of childhood ALL to date have focused on inherited genetic effects; however, maternal genetic effects (the role of the maternal genotype on phenotype development in the offspring) also may play a role in ALL susceptibility.

METHODS:

The authors conducted a family-based exome-wide association study of maternal genetic effects among Hispanics with childhood B-cell ALL using the Illumina Infinium HumanExome BeadChip. A discovery cohort of 312 Guatemalan and Hispanic American families and an independent replication cohort of 152 Hispanic American families were used.

RESULTS:

Three maternal single-nucleotide polymorphisms (SNPs) approached the study threshold for significance after correction for multiple testing (P<1.0 × 10-6 ): MTL5 rs12365708 (testis expressed metallothionein-like protein [tesmin]) (relative risk [RR], 2.62; 95% confidence interval [95% CI], 1.61-4.27 [P = 1.8 × 10-5 ]); ALKBH1 rs6494 (AlkB homolog 1, histone H2A dioxygenase) (RR, 3.77; 95% CI, 1.84-7.74 [P = 3.7 × 10-5 ]); and NEUROG3 rs4536103 (neurogenin 3) (RR, 1.75; 95% CI, 1.30-2.37 [P = 1.2 × 10-4 ]). Although effect sizes were similar, these SNPs were not nominally significant in the replication cohort in the current study. In a meta-analysis comprised of the discovery cohort and the replication cohort, these SNPs were still not found to be statistically significant after correction for multiple comparisons (rs12365708: pooled RR, 2.27 [95% CI, 1.48-3.50], P = 1.99 × 10-4 ; rs6494: pooled RR, 2.31 [95% CI, 1.38-3.85], P = .001; and rs4536103: pooled RR, 1.67 [95% CI, 1.29-2.16] P = 9.23 × 10-5 ).

CONCLUSIONS:

In what to the authors' knowledge is the first family-based based exome-wide association study to investigate maternal genotype effects associated with childhood ALL, the results did not implicate a strong role of maternal genotype on disease risk among Hispanics; however, 3 maternal SNPs were identified that may play a modest role in susceptibility. Cancer 2016;122:3697-704. © 2016 American Cancer Society.

KEYWORDS:

Hispanics; acute lymphoblastic leukemia (ALL); childhood ALL; exome; genetic epidemiology; maternal genetics

PMID:
27529658
PMCID:
PMC5115939
DOI:
10.1002/cncr.30241
[Indexed for MEDLINE]
Free PMC Article

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