Identification of a novel susceptibility locus at 16q23.1 associated with childhood acute lymphoblastic leukemia in Han Chinese.
Recently, genome-wide association studies (GWAS) have identified several susceptibility loci for childhood acute lymphoblastic leukemia (ALL) in populations of European descent; only a few loci could be confirmed in Asian populations because of those populations' genetic heterogeneity. To identify genetic factors associated with childhood ALL risk in the Chinese population, we performed a three-stage GWAS of 1184 childhood ALL cases and 3219 non-ALL controls. The combined analysis identified a new locus (rs1121404 in WWOX) at 16q23.1 associated with childhood ALL susceptibility (odds ratio (OR) = 1.38, P = 5.29 × 10-10), especially in the subtype of B-ALL (OR = 1.39, P = 2.47 × 10-9). The functional studies subsequently revealed that the expression of WWOX in ALL bone marrow was significantly lower than that in normal bone marrow. The G allele of rs1121404 displayed significantly decreased levels of mRNA expression of WWOX These results suggest that WWOX plays an important role in the development of childhood ALL and provide new insights into the etiology of childhood ALL.
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200030, China shiyongyong@gmail.com zdzhang@njmu.edu.cn mwang@njmu.edu.cn.|The Affiliated Hospital of Qingdao University, Qingdao 266003, China.|Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
Yongyong
Y
Shi
Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.|Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
Mulong
M
Du
Department of Hematology and Oncology, Nanjing Children's Hospital Affiliated with Nanjing Medical University, Nanjing 210000, China.
Yongjun
Y
Fang
Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.|Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
Na
N
Tong
Department of Hematology and Oncology, Children's hospital of Fudan University, Shanghai 200032, China.
Xiaowen
X
Zhai
Department of Children's healthcare, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China.
Xiaojing
X
Sheng
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200030, China.|Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
Zhiqiang
Z
Li
Department of Hematology and Oncology, Nanjing Children's Hospital Affiliated with Nanjing Medical University, Nanjing 210000, China.
Yao
Y
Xue
Department of Hematology and Oncology, The Affiliated Children's Hospital of Soochow University, Suzhou 215025, China.
Jie
J
Li
Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.|Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
Haiyan
H
Chu
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200030, China.|Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
Jianhua
J
Chen
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200030, China.|Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
Zhijian
Z
Song
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200030, China.|Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
Jiawei
J
Shen
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200030, China.
Jue
J
Ji
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200030, China.
Xingwang
X
Li
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Zhibin
Z
Hu
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Hongbing
H
Shen
Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, Illinois 60201, USA.
Jianfeng
J
Xu
Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China shiyongyong@gmail.com zdzhang@njmu.edu.cn mwang@njmu.edu.cn.|Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
Meilin
M
Wang
Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China shiyongyong@gmail.com zdzhang@njmu.edu.cn mwang@njmu.edu.cn.|Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
Zhengdong
Z
Zhang
D000483:Alleles; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002681:China; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D016017:Odds Ratio; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D000074584:WW Domain-Containing Oxidoreductase
D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human