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

• Published in: Scientific reports 2018-01, Vol.8 (1), p.789-9, Article 789
• Main Authors: Urayama, Kevin Y., Takagi, Masatoshi, Kawaguchi, Takahisa, Matsuo, Keitaro, Tanaka, Yoichi, Ayukawa, Yoko, Arakawa, Yuki, Hasegawa, Daisuke, Yuza, Yuki, Kaneko, Takashi, Noguchi, Yasushi, Taneyama, Yuichi, Ota, Setsuo, Inukai, Takeshi, Yanagimachi, Masakatsu, Keino, Dai, Koike, Kazutoshi, Toyama, Daisuke, Nakazawa, Yozo, Kurosawa, Hidemitsu, Nakamura, Kozue, Moriwaki, Koichi, Goto, Hiroaki, Sekinaka, Yujin, Morita, Daisuke, Kato, Motohiro, Takita, Junko, Tanaka, Toshihiro, Inazawa, Johji, Koh, Katsuyoshi, Ishida, Yasushi, Ohara, Akira, Mizutani, Shuki, Matsuda, Fumihiko, Manabe, Atsushi
• Format: Article
• Language: English
• Subjects: 45/22; 45/43; 631/208/205/2138; 631/67/2324; 692/699/67/2332; Acute lymphoblastic leukemia; Adolescent; Asian Continental Ancestry Group - genetics; Cancer; Child; Child, Preschool; Children; Deoxyribonucleic acid; DNA; DNA microarrays; DNA-Binding Proteins - genetics; Female; Genetic Loci; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genotyping; Humanities and Social Sciences; Humans; Ikaros Transcription Factor - genetics; Infant; Infant, Newborn; Japan; Leukemia; Linkage Disequilibrium; Lymphatic leukemia; Lymphocytes B; Male; multidisciplinary; Phosphotransferases (Alcohol Group Acceptor) - genetics; Polymorphism, Single Nucleotide; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Transcription Factors - genetics; Young Adult
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-19127-7

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 PIP4K 2 A (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.