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Late Effects

Second Malignant Neoplasm (SMN)




The risk of a second malignant neoplas (SMN) and the type of SMN depend on:

1. The original diagnosis:

The following primary diagnoses are most often associated with development of SMNs:

2. Type of therapy received:

  • Alkylating agents and radiation therapy (RT) associated with increased risk of SMN

3. Age at diagnosis

  • Younger age at diagnosis associated with an increased risk of SMN after RT

4. Genetic predisposition

  • Bilateral retinoblastoma patients have a very increased risk of SMN4
  • Family history of cancer and primary soft tissue sarcoma predisposes to SMN
  • Li-Fraumeni syndrome:
    • germ line mutation in tumor suppressor genes
  • Polymorphism in drug metabolizing enzymes such as thiopurine S-methyltransferase (TPMT)
    • TPMT catalyses the S-methylation of thiopurines such as 6-mercaptopurine
    • TPMT activity exhibits genetic polymorphism
    • TPMT deficiency is an autosomal recessive trait.
    • TPMT genotype may influence the risk of development of a SMN

5. Gender

  • Females at increased risk (excess breast and thyroid cancers)

6. Life style factors:

  • Tobacco
    • Smoking significantly increases the risk of either alkylating agent-associated or RT-associated lung cancer
  • Diet
  • Hormonal factors
  • Alcohol
    • Risk factor for oral, esophageal and liver cancers



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