Abstract 1658P
Background
Patients with thyroid carcinomas usually exhibits heterogenous response to radioiodine therapy, however, the genetic contribution to this heterogenous response hasn’t been well studied. In this study, we aimed to screen for radioiodine uptake-related SNP sites from a list of 41 well-studied drug related SNP sites.
Methods
A retrospective study was conducted in Peking Union Medical Hospital to evaluate 106 thyroid carcinomas samples. The efficacy of RAI uptake was classified into as followed: 1) the malignant/metastatic tissue does not ever concentrate radioactive iodine (RAI); 2) the tumor tissue loses the ability to concentrate RAI after previous evidence of RAI-avid disease; 3) RAI is concentrated in some lesions but not in others; 4) metastatic disease progresses despite significant concentration of RAI;. All samples were targeted sequenced on the commercial panel ThyroLeadTM which covered 24 common thyroid malignancy genes as well as 41 drug-related SNPs. Manual inspection was performed to remove samples with indetermined RAI uptake subgroups (47 samples). All sequencing data was quality checked to ensure at least 30 individual reads was covered on SNPs. The association between known SNPs and RAI uptake subgroups was determined by Fisher’s exact test followed by Bonferroni correction.
Results
Eventually, SNP rs4646, which was located on gene CYP19A1 and reported to be associated with the response to several hormonal drugs, exhibited a strong correlation with RAI uptake in this study (p-value = 0.000123 ). Comparing with effective uptake subgroups, allele G/G and allele T/G are more frequently observed in subgroup 1) (n = 18; 9) and 2) (n = 11; 6) than other subgroups (n = 2; 7).
Conclusions
In conclusion, our results provided a novel insight into understanding the genetic contribution to the efficacy of RAI uptake. Due to limited sample size, further prospectively studies and cellular studies are needed to assess the biological functions of rs4646.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.