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Cancer Health Center

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Late Effects of Treatment for Childhood Cancer (PDQ®): Treatment - Health Professional Information [NCI] - Subsequent Neoplasms


Subsequent Neoplasms and Genetic Susceptibility

Literature clearly supports the role of chemotherapy and radiation in the development of SNs. However, interindividual variability exists, suggesting that genetic variation has a role in susceptibility to genotoxic exposures, or that genetic susceptibility syndrome confers an increased risk of cancer, such as Li-Fraumeni syndrome. Previous studies have demonstrated that childhood cancer survivors with either a family history of cancer, but more so, presence of Li-Fraumeni syndrome, carry an increased risk of developing an SN.[58,59]

The risk of SNs could potentially be modified by mutations in high-penetrance genes that lead to these serious genetic diseases (e.g., Li-Fraumeni syndrome).[59] However, the attributable risk is expected to be very small because of the extremely low prevalence of mutations in high-penetrance genes.

Table 1 below summarizes the spectrum of neoplasms, affected genes, and Mendelian mode of inheritance of selected syndromes of inherited cancer predisposition.

Table 1. Selected Syndromes of Inherited Cancer Predispositiona

SyndromeMajor Tumor TypesAffected GeneMode of Inheritance
AML = acute myeloid leukemia; MDS = myelodysplastic syndromes; WAGR = Wilms tumor, aniridia, genitourinary anomalies, mental retardation.
a Adapted from Strahm et al.[60]
b Dominant in a fraction of patients, spontaneous mutations can occur.
Adenomatous polyposis of the colonColon, hepatoblastoma, intestinal cancers, stomach, thyroid cancerAPCDominant
Ataxia-telangiectasiaLeukemia, lymphomaATMRecessive
Beckwith-Wiedemann syndromeAdrenal carcinoma, hepatoblastoma, rhabdomyosarcoma, Wilms tumorCDKN1C/NSD1Dominant
Bloom syndromeLeukemia, lymphoma, skin cancerBLMRecessive
Diamond-Blackfan anemiaColon cancer, osteogenic sarcoma, AML/MDSRPS19and otherRPgenesDominant, spontaneousb
Fanconi anemiaGynecological tumors, leukemia, squamous cell carcinomaFANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCGRecessive
Juvenile polyposis syndromeGastrointestinal tumorsSMAD4/DPC4Dominant
Li-Fraumeni syndromeAdrenocortical carcinoma, brain tumor, breast carcinoma, leukemia, osteosarcoma, soft tissue sarcomaTP53Dominant
Multiple endocrine neoplasia 1Pancreatic islet cell tumor, parathyroid adenoma, pituitary adenomaMEN1Dominant
Multiple endocrine neoplasia 2Medullary thyroid carcinoma, pheochromocytomaRETDominant
Neurofibromatosis type 1Neurofibroma, optic pathway glioma, peripheral nerve sheath tumorNF1Dominant
Neurofibromatosis type 2Vestibular schwannomaNF2Dominant
Nevoid basal cell carcinoma syndromeBasal cell carcinoma, medulloblastomaPTCHDominant
Peutz-Jeghers syndromeIntestinal cancers, ovarian carcinoma, pancreatic carcinomaSTK11Dominant
RetinoblastomaOsteosarcoma, retinoblastomaRB1Dominant
Tuberous sclerosisHamartoma, renal angiomyolipoma, renal cell carcinomaTSC1/TSC2Dominant
von Hippel-Lindau syndromeHemangioblastoma, pheochromocytoma, renal cell carcinoma, retinal and central nervous tumorsVHLDominant
WAGR syndromeGonadoblastoma, Wilms tumorWT1Dominant
Wilms tumor syndromeWilms tumorWT1Dominant
Xeroderma pigmentosumLeukemia, melanomaXPA, XPB, XPC, XPD, XPE, XPF, XPG, POLHRecessive
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