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Sci Rep. 2018 Jan 15;8(1):789. doi: 10.1038/s41598-017-19127-7.

Regional evaluation of childhood acute lymphoblastic leukemia genetic susceptibility loci among Japanese.

Author information

1
Department of Social Medicine, National Center for Child Health and Development, Tokyo, Japan. urayama-k@ncchd.go.jp.
2
Graduate School of Public Health, St. Luke's International University, Tokyo, Japan. urayama-k@ncchd.go.jp.
3
Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.
4
Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
5
Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Aichi, Japan.
6
Department of Clinical Pharmacy, Center for Clinical Pharmacy and Sciences, School of Pharmacy, Kitasato University, Tokyo, Japan.
7
Department of Social Medicine, National Center for Child Health and Development, Tokyo, Japan.
8
Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.
9
Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan.
10
Department of Hematology/Oncology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
11
Department of Pediatrics, Japanese Red Cross Narita Hospital, Chiba, Japan.
12
Department of Hematology/Oncology, Chiba Children's Hospital, Chiba, Japan.
13
Department of Pediatrics, Teikyo University Chiba Medical Center, Chiba, Japan.
14
Department of Pediatrics, University of Yamanashi, Yamanashi, Japan.
15
Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
16
Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, Japan.
17
Division of Pediatric Hematology and Oncology, Ibaraki Children's Hospital, Mito, Japan.
18
Division of Pediatrics, Showa University Fujigaoka Hospital, Yokohama, Japan.
19
Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
20
Department of Pediatrics, Dokkyo Medical University, Tochigi, Japan.
21
Department of Pediatrics, Teikyo University Hospital, Tokyo, Japan.
22
Department of Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
23
Division of Hematology/Oncology & Regenerative Medicine, Kanagawa Children's Medical Center, Yokohama, Japan.
24
Department of Pediatrics, National Defense Medical College, Saitama, Japan.
25
Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
26
Department of Pediatrics, The University of Tokyo Hospital, Tokyo, Japan.
27
Department of Human Genetics and Disease Diversity, Tokyo Medical Dental University, Tokyo, Japan.
28
Bioresource Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
29
Pediatric Medical Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.
30
Department of Pediatrics, Toho University, Tokyo, Japan.

Abstract

Genome-wide association studies (GWAS) performed mostly in populations of European and Hispanic ancestry have confirmed an inherited genetic basis for childhood acute lymphoblastic leukemia (ALL), but these associations are less clear in other races/ethnicities. DNA samples from ALL patients (aged 0-19 years) previously enrolled onto a Tokyo Children's Cancer Study Group trial were collected during 2013-2015, and underwent single nucleotide polymorphism (SNP) microarray genotyping resulting in 527 B-cell ALL for analysis. Cases and control data for 3,882 samples from the Nagahama Study Group and Aichi Cancer Center Study were combined, and association analyses across 10 previous GWAS-identified regions were performed after targeted SNP imputation. Linkage disequilibrium (LD) patterns in Japanese and other populations were evaluated using the varLD score based on 1000 Genomes data. Risk associations for ARID5B (rs10821936, OR = 1.84, P = 6 × 10-17) and PIP4K2A (rs7088318, OR = 0.76, P = 2 × 10-4) directly transferred to Japanese, and the IKZF1 association was detected by an alternate SNP (rs1451367, OR = 1.52, P = 2 × 10-6). Marked regional LD differences between Japanese and Europeans was observed for most of the remaining loci for which associations did not transfer, including CEBPE, CDKN2A, CDKN2B, and ELK3. This study represents a first step towards characterizing the role of genetic susceptibility in childhood ALL risk in Japanese.

PMID:
29335448
PMCID:
PMC5768812
DOI:
10.1038/s41598-017-19127-7
[Indexed for MEDLINE]
Free PMC Article

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