Second Malignant Neoplasm (SMN)
Etiology
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:
- Hereditary retinoblastoma
- Hodgkin lymphoma
- Soft tissue sarcoma
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
