Associations between RET tagSNPs and their haplotypes and susceptibility, clinical severity, and thyroid function in patients with differentiated thyroid cancer

BACKGROUND: It is unclear whether common genetic variants of the RET proto-oncogene contribute to disease susceptibility, clinical severity, and thyroid function in differentiated thyroid cancer (DTC). METHODS: A total of 300 DTC patients and 252 healthy controls were enrolled in this study. Seven RET tagging single nucleotide polymorphisms were genotyped using the KASPar platform. RESULTS: Subgroup analysis showed that concomitant thyroid benign diseases were less likely to occur in DTC subjects with the rs1799939 AG or AG plus AA genotypes (odds ratio (OR) = 1.93 and 1.88, P = 0.009 and 0.011, respectively). A rare haplotype, CGGATAA, was associated statistically with a reduced risk of DTC (OR = 0.18, P = 0.001). Concerning the aggressive features of DTC, higher level of N stage was more likely to occur in subjects carrying the wild-type genotypes at rs1800860 site (for dominant model: OR = 0.48, P = 0.008). Another rare haplotype, CAAGCGT, conferred increased risk for the occurrence of distant metastasis (OR = 7.57, P = 0.009). Notably, higher thyroid stimulating hormone levels and lower parathyroid hormone levels were found in patients with rs2075912, rs2565200, and rs2742240 heterozygotes and rare homozygotes; similar results were observed between PTH levels and rs1800858. CONCLUSION: This study provided useful information on RET variants that should be subjected to further study.