Work

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

Year: 2016

Type: article

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.

Source: Cancer

DOI: 10.1002/cncr.30241