Dataset Information

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

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.

SUBMITTER: Urayama KY

PROVIDER: S-EPMC5768812 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Urayama Kevin Y KY Takagi Masatoshi M Kawaguchi Takahisa T Matsuo Keitaro K Tanaka Yoichi Y Ayukawa Yoko Y Arakawa Yuki Y Hasegawa Daisuke D Yuza Yuki Y Kaneko Takashi T Noguchi Yasushi Y Taneyama Yuichi Y Ota Setsuo S Inukai Takeshi T Yanagimachi Masakatsu M Keino Dai D Koike Kazutoshi K Toyama Daisuke D Nakazawa Yozo Y Kurosawa Hidemitsu H Nakamura Kozue K Moriwaki Koichi K Goto Hiroaki H Sekinaka Yujin Y Morita Daisuke D Kato Motohiro M Takita Junko J Tanaka Toshihiro T Inazawa Johji J Koh Katsuyoshi K Ishida Yasushi Y Ohara Akira A Mizutani Shuki S Matsuda Fumihiko F Manabe Atsushi A

Scientific reports 20180115 1

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 5 ...[more]

PMID: 29335448

Similar Datasets

Project description:Acute lymphoblastic leukemia is the major pediatric cancer in developed countries. To date most association studies of acute lymphoblastic leukemia have been based on the candidate gene approach and have evaluated a restricted number of polymorphisms. Such studies have served to highlight difficulties in conducting statistically and methodologically rigorous investigations into acute lymphoblastic leukemia risk. Recent genome-wide association studies of childhood acute lymphoblastic leukemia have provided robust evidence that common variation at four genetic loci confers a modest increase in risk. The accumulated experience to date and relative lack of success of initial efforts to identify novel acute lymphoblastic leukemia predisposition loci emphasize the need for alternative study designs and methods. The International Childhood Acute Lymphoblastic Leukaemia Genetics Consortium includes 12 research groups in Europe, Asia, the Middle East and the Americas engaged in studying the genetics of acute lymphoblastic leukemia. The initial goal of this consortium is to identify and characterize low-penetrance susceptibility variants for acute lymphoblastic leukemia through association-based analyses. Efforts to develop genome-wide association studies of acute lymphoblastic leukemia, in terms of both sample size and single nucleotide polymorphism coverage, and to increase the number of single nucleotide polymorphisms taken forward to large-scale replication should lead to the identification of additional novel risk variants for acute lymphoblastic leukemia. Ethnic differences in the risk of acute lymphoblastic leukemia are well recognized and thus in assessing the interplay between inherited and non-genetic risk factors, analyses using different population cohorts with different incidence rates are likely to be highly informative. Given that the frequency of many acute lymphoblastic leukemia subgroups is small, identifying differential effects will realistically only be possible through multi-center pooled analyses. Here, we review the rationale for identifying genetic risk variants for acute lymphoblastic leukemia and our proposed strategy for establishing the International Childhood Acute Lymphoblastic Leukaemia Genetics Consortium.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets