Table 1.
Genes associated with risk for hematopoietic plus other cancers
| Gene(s) | Condition | Hematopoietic cancer(s) | Prevalence of hematopoietic cancers36-39 | Other cancers | Other features |
|---|---|---|---|---|---|
| ATM | Ataxia telangiectasia | ALL, lymphoma | ∼30-40% | Breast | Immunodeficiency |
| Ovarian | Cerebellar ataxia, oculomotor apraxia | ||||
| Gastric | Choreoathetosis | ||||
| Others | Telangiectasias | ||||
| BLM | Bloom syndrome | ALL, AML/MDS, lymphoma | 15% | GI | Pre- and postnatal growth deficiency |
| Breast | Short stature | ||||
| Respiratory | Butterfly rash | ||||
| Skin | GERD | ||||
| Others | Early-onset menopause | ||||
| Male infertility | |||||
| Early-onset diabetes | |||||
| COPD | |||||
| FANCA-P | Fanconi anemia | ALL, AML/MDS | 7-13% AML 500-fold increase in risk | H/N SCC | Bone marrow failure |
| Skin | Short stature | ||||
| GI | Hyper-/hypopigmentation | ||||
| Genital | Skeletal anomalies | ||||
| Liver | Ocular, renal, gonadal abnormalities | ||||
| Brain | DD | ||||
| Chemotherapy and/or radiation toxicity | |||||
| (Note: Absence of physical findings in 25-40%) | |||||
| MLH1, MSH2, MSH6, PMS2 | Constitutional mismatch repair deficiency | ALL, AML, lymphoma | ∼33% | Brain | Cafe au lait macules |
| Colorectal/GI | Hypopigmentation | ||||
| Endometrial | Other NF1 signs | ||||
| Others | Pilomatricoma | ||||
| GI polyps | |||||
| Mild immunoglobulin class switch defects | |||||
| Multiple | Dyskeratosis congenita | AML/MDS | 3-33% | H/N SCC | Dysplastic nails |
| Skin | Lacy reticular pigmentation | ||||
| Anogenital | Other pigmentation | ||||
| Oral leukoplakia | |||||
| Premature graying/alopecia | |||||
| Pulmonary fibrosis | |||||
| Eye and dental abnormalities | |||||
| Multiple | Diamond-Blackfan anemia | ALL, AML/MDS, lymphoma | ∼4-5% | Osteosarcoma | Macrocytic anemia |
| Congenital malformations (craniofacial, limb, heart, genitourinary) | |||||
| Growth retardation | |||||
| NBN | Nijmegen breakage syndrome | ALL, lymphoma | 40% | MBL | Microcephaly |
| Glioma | Short stature | ||||
| RMS | Recurrent infections | ||||
| Characteristic facies | |||||
| Hyper- or hypopigmentation | |||||
| Premature ovarian failure | |||||
| Decline in intellectual ability | |||||
| NF1 | Neurofibromatosis 1 | JMML, CMML, AML/MDS | AML/MDS: 11% | OPG | Cafe au lait macules |
| JMML: 200-500-fold higher than general population | Brain tumor | Inguinal/axillary freckling | |||
| MPNST | Lisch nodules | ||||
| GIST | Neurofibroma | ||||
| Breast | Tibial dysplasia | ||||
| Vasculopathy | |||||
| Learning disabilities | |||||
| PTPN11 | Noonan syndrome | JMML, CMML, AML, ALL, TMD | ∼1% | RMS | Characteristic facies |
| Brain | Heart defect (especially pulmonary valve stenosis) | ||||
| DD | |||||
| Short stature | |||||
| Coagulation defects | |||||
| Skeletal and ocular abnormalities | |||||
| RECQL4 | Rothmund-Thomson syndrome | AML/MDS | Unknown | Osteosarcoma | Poikiloderma |
| Skin | Sparse hair | ||||
| Short stature | |||||
| Cataracts | |||||
| Skeletal/dental abnormalities | |||||
| Cataracts | |||||
| TP53 | Li-Fraumeni syndrome | ALL (especially low hypodiploid), AML/MDS lymphoma | 2-4% | Breast | None |
| Brain | |||||
| Sarcoma | |||||
| ACC | |||||
| Others | |||||
| WRN | Werner syndrome | AML/MDS | Unknown | Sarcoma | Premature aging with onset in first decade |
| Melanoma | Early-onset diabetes, osteoporosis | ||||
| Thyroid | MI |
ACC, adrenocortical carcinoma; CMML, chronic myelomonocytic leukemia; COPD, chronic obstructive pulmonary disease; DD, developmental delay; GERD, gastroesophageal reflux disease; GI, gastrointestinal tract; GIST, gastrointestinal stromal tumor; H/N SCC, head/neck squamous cell carcinoma; JMML, juvenile myelomonocytic leukemia; MBL, medulloblastoma; MI, myocardial infarction; MPNST, malignant peripheral nerve sheath tumor; OPG, optic pathway glioma; RMS, rhabdomyosarcoma; TMD, transient myeloproliferative disorder.