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Nat Commun. 2018 Apr 9;9(1):1340. doi: 10.1038/s41467-018-03178-z.

Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia.

Author information

1
Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey, SM2 5NG, UK.
2
Division of Molecular Genetic Epidemiology, German Cancer Research Centre, 69120, Heidelberg, Germany.
3
Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
4
Wolfson Childhood Cancer Research Centre, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.
5
Department of Haematology, Great Ormond Street Hospital, London, WC1N 3JH, UK.
6
Department of Health Sciences, University of York, York, YO10 5DD, UK.
7
Department of Paediatric and Adolescent Haematology and Oncology, Leeds General Infirmary, Leeds, LS1 3EX, UK.
8
Medical Genetics Research Group, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, LS9 7TF, UK.
9
Paediatric and Familial Cancer Research Group, Institute of Cancer Sciences, St. Mary's Hospital, Manchester, M13 9WL, UK.
10
Department of Human Genetics, Institute of Human Genetics, University of Heidelberg, 69120, Heidelberg, Germany.
11
Department of Genomics, Institute of Human Genetics, Life & Brain Centre, University of Bonn, D-53012, Bonn, Germany.
12
Department of Biomedicine, Human Genomics Research Group, University Hospital and University of Basel, 4031, Basel, Switzerland.
13
Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, 45147, Essen, Germany.
14
Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, CB1 8RN, UK.
15
Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, CB1 8RN, UK.
16
Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Laboratory, Cambridge, CB1 8RN, UK.
17
Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
18
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
19
Division of Breast Cancer Research, The Institute of Cancer Research, London, SW7 3RP, UK.
20
Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK.
21
Institute of Population Health, University of Manchester, Manchester, M13 9PL, UK.
22
Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
23
Department of Applied Health Research, University College London, London, WC1E 7HB, UK.
24
Centre for Evolution and Cancer, Institute of Cancer Research, Sutton, Surrey, SM2 5NG, UK.
25
Department of Paediatric Haematology and Oncology, Hannover Medical School, 30625, Hannover, Germany.
26
General Paediatrics, University Hospital Schleswig-Holstein, 24105, Kiel, Germany.
27
Center for Primary Health Care Research, Lund University, 221 00, Lund, Sweden.
28
Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey, SM2 5NG, UK. richard.houlston@icr.ac.uk.

Abstract

Genome-wide association studies (GWAS) have advanced our understanding of susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL); however, much of the heritable risk remains unidentified. Here, we perform a GWAS and conduct a meta-analysis with two existing GWAS, totaling 2442 cases and 14,609 controls. We identify risk loci for BCP-ALL at 8q24.21 (rs28665337, P = 3.86 × 10-9, odds ratio (OR) = 1.34) and for ETV6-RUNX1 fusion-positive BCP-ALL at 2q22.3 (rs17481869, P = 3.20 × 10-8, OR = 2.14). Our findings provide further insights into genetic susceptibility to ALL and its biology.

PMID:
29632299
PMCID:
PMC5890276
DOI:
10.1038/s41467-018-03178-z
[Indexed for MEDLINE]
Free PMC Article

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