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Inherited genetic variation in childhood acute lymphoblastic leukemia

Takaya Moriyama, Mary V. Relling and Jun J. Yang

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Tables

  • Table 1

    Examples of germline genetic variants associated with ALL susceptibility, treatment outcomes, and toxicities of ALL therapy

    GeneSNP IDStudy designPhenotypeSample size (N)Odds ratio (95% CI)PReference
    ALL susceptibility
    ARID5Brs7089424GWASALL risk9071.65 (1.54-1.76)6.7 × 10−1927
    rs10821936GWAS4411.91 (1.6-2.2)1.4 × 10−1528
    IKZF1rs4132601GWASALL risk9071.69 (1.58-1.81)1.2 × 10−1927
    rs11978267GWAS4411.69 (1.4-1.9)8.8 × 10−1128
    CEBPErs2239633GWASALL risk9071.34 (1.22-1.45)2.9 × 10−727
    CDKN2Ars17756311GWASALL risk24501.36 (1.18-1.56)1.4 × 10−530
    PIP4K2Ars7088318GWASALL risk24501.40 (1.28-1.53)1.1 × 10−1130
    GATA3rs3824662GWASALL risk31071.31 (1.21-1.41)8.6 × 10−1231
    GWASRisk for Ph-like ALL5113.85 (2.7-5.4)2.2 × 10−1432
    TP63rs17505102GWASRisk for ETV6-RUNX1 ALL13700.65 (0.52-0.75)8.9 × 10−939
    Treatment outcome
    TPMTrs1800462Candidate geneMinimal residual disease8140.34 (0.13-0.86).0244
    rs1800460
    rs1142345
    rs1800460Candidate geneRelapse6010.36 (0.15-0.88).0345
    rs1142345
    IL15rs17007695GWASMinimal residual disease4872.67 (1.53-4.68)8.9 × 10−755
    PYGLrs7142143GWASRelapse25353.61 (2.34-5.57)6.7 × 10−958
    PDE4Brs6683977GWASRelapse25351.41 (1.22-1.64)5.1 × 10−658
    GATA3rs3824662GWASRelapse7811.43 (1.10-1.86).00732
    Minimal residual disease7101.38 (1.03-1.83).039
    GWASRelapse22582.0 (1.71-3.66)2.3 × 10−631
    Toxicities
    TPMTrs1800462Candidate geneThiopurine-induced myelosuppression1809.3 (3.58-24.27).00768
    rs1800460
    rs1142345
    NUDT15rs116855232GWASThiopurine intolerance657*8.8 × 10−970
    ACP1rs12714403GWASGlucocorticoid-induced osteonecrosis3625.6 (2.7-11.3)1.9 × 10−680
    GRIA1rs4958351GWASAsparaginase allergy4851.75 (1.41-2.17)3.5 × 10−784
    HLA-DRB1HLA-DRB1*07:01Candidate geneAsparaginase allergy18701.64 (1.28-2.09)7.5 × 10−586
    Anti-asparaginase antibody5022.92 (1.82-4.80)1.4 × 10−5
    ASNSrs3832526Candidate geneAsparaginase allergy53314.6 (3.6-58.7)<.000587
    Asparaginase pancreatitis8.6 (2.0-37.3).008
    CBR3rs1056892Candidate geneAnthracycline-induced cardiomyopathy4871.79 (1.08-2.96).0288
    HAS3rs2232228GWASAnthracycline-induced cardiomyopathy3623.7 (1.3-10.2).0589
    CEP72rs924607GWASVincristine-induced neuropathy321*4.7 × 10−890
    SLCO1B1rs11045879GWASMethotrexate clearance640*8.2 × 10−11104, 105
    Methotrexate-induced GI toxicity20616.4 (8.7-26.7).004
    Candidate geneMethotrexate clearance115*.008106
    rs4149056Candidate geneMethotrexate clearance415*3.5 × 10−450
    • CI, confidence interval; GI, gastrointestinal; GWAS, genome-wide association study; ID, identification; Ph, Philadelphia chromosome; SNP, single-nucleotide polymorphism.