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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

Syndrome Major Tumor Types Affected Gene Mode 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 colon Colon, hepatoblastoma, intestinal cancers, stomach, thyroid cancer APC Dominant
Ataxia-telangiectasia Leukemia, lymphoma ATM Recessive
Beckwith-Wiedemann syndrome Adrenal carcinoma, hepatoblastoma, rhabdomyosarcoma, Wilms tumor CDKN1C/NSD1 Dominant
Bloom syndrome Leukemia, lymphoma, skin cancer BLM Recessive
Diamond-Blackfan anemia Colon cancer, osteogenic sarcoma, AML/MDS RPS19and otherRPgenes Dominant, spontaneousb
Fanconi anemia Gynecological tumors, leukemia, squamous cell carcinoma FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG Recessive
Juvenile polyposis syndrome Gastrointestinal tumors SMAD4/DPC4 Dominant
Li-Fraumeni syndrome Adrenocortical carcinoma, brain tumor, breast carcinoma, leukemia, osteosarcoma, soft tissue sarcoma TP53 Dominant
Multiple endocrine neoplasia 1 Pancreatic islet cell tumor, parathyroid adenoma, pituitary adenoma MEN1 Dominant
Multiple endocrine neoplasia 2 Medullary thyroid carcinoma, pheochromocytoma RET Dominant
Neurofibromatosis type 1 Neurofibroma, optic pathway glioma, peripheral nerve sheath tumor NF1 Dominant
Neurofibromatosis type 2 Vestibular schwannoma NF2 Dominant
Nevoid basal cell carcinoma syndrome Basal cell carcinoma, medulloblastoma PTCH Dominant
Peutz-Jeghers syndrome Intestinal cancers, ovarian carcinoma, pancreatic carcinoma STK11 Dominant
Retinoblastoma Osteosarcoma, retinoblastoma RB1 Dominant
Tuberous sclerosis Hamartoma, renal angiomyolipoma, renal cell carcinoma TSC1/TSC2 Dominant
von Hippel-Lindau syndrome Hemangioblastoma, pheochromocytoma, renal cell carcinoma, retinal and central nervous tumors VHL Dominant
WAGR syndrome Gonadoblastoma, Wilms tumor WT1 Dominant
Wilms tumor syndrome Wilms tumor WT1 Dominant
Xeroderma pigmentosum Leukemia, melanoma XPA, XPB, XPC, XPD, XPE, XPF, XPG, POLH Recessive
1 | 2 | 3 | 4 | 5 | 6
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