Hypothalamic-pituitary deficiency after radiation in childhood cancer survivors is associated with rare variants in TNS2
Main finding · HP deficienciesResult — go to the resultRate ratio 2.72 95% CI 1.81–4.09Authors' conclusion
TNS2 may contribute to radiation-induced HP deficiencies.
Study context
- Population
- 5-year childhood cancer survivors exposed to HP-RT, St. Jude Lifetime Cohort; median follow-up 31.9 years; replication in 1328 Childhood Cancer Survivor Study (CCSS) survivors801 analysed
- Participants
- 809 survivors
- Exposure
- TNS2 rare-variant carriers vs non-carriers
- Outcome
- Hypothalamic-pituitary (HP) deficiency rate (total counts/person-year): GHD, LH/FSHD, TSHD, ACTHD
Methodological detailswhole-exome sequencing rare-variant analysis, GWAS, replication cohort
- Whole-exome sequencing rare-variant analysis
- GWAS
- Replication cohort
Main finding
HP deficiencies
Rate ratio
2.72
95% CI 1.81–4.09
P = 1.5 × 10-5
TNS2 carriersvs Non-carriers
rate ratio 2.72 (95% CI 1.81–4.09); P = 1.5 × 10-5
As reported in the abstract
Observational data: associations, not effects.
Further findings
| Outcome | Estimate | |
|---|---|---|
| Individual HP deficienciesTNS2 carriersvs Non-carriers | rate ratio, LH/FSHD 3.31 (CI 1.28–7.99) | |
| Individual HP deficienciesTNS2 carriersvs Non-carriers | rate ratio, TSHD 5.29 (CI 2.42–11.34) | |
| Individual HP deficienciesTNS2 carriersvs Non-carriers | rate ratio, ACTHD 3.97 (CI 1.05–12.31) | |
| 0.050.21520Ratio (log scale) |
GWAS (606 survivors of European ancestry, MAF ≥ 0.01)
- No statistically significant variants in GWAS
Original publication
Hypothalamic-pituitary deficiency after radiation in childhood cancer survivors is associated with rare variants in TNS2. J Clin Endocrinol Metab. Published 25 February 2026. doi:10.
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