Genetic variations in amino acid metabolism-related genes are associated with risk of papillary thyroid carcinoma: a case-control study.

BACKGROUND: Abnormal amino acid metabolic pathways, especially those of glutamine, serine and proline, are crucial to tumourigenesis and the development of papillary thyroid carcinoma (PTC). However, genetic variants in key genes regulating these metabolic pathways remain poorly characterized in PTC. METHODS: Seven SNPs in the SLC1A5, SLC1A3, SHMT1, and PRODH genes were genotyped in 620 patients with PTC and 620 controls using a flight mass spectrometry platform. RESULTS: The frequency of the minor allele A of SLC1A5-rs2070246 was significantly greater in the PTC group than in the control group, thereby increasing the risk of PTC by 1.587 times (p < 0.0001). Similarly, the minor alleles C, T and A of SLC1A3-rs16903247, SHMT1-rs4925166 and PRODH-rs372055 increased susceptibility to PTC by 2.584, 1.346 and 1.349 times, respectively (prs16903247 < 0.0001, prs4925166 = 0.00024, and prs372055= 0.001, respectively). Moreover, carriers of the rs2070246-GA/AA genotype had a 1.77- and 2.35-fold increased risk of PTC, and the rs16903247-PTC/CC genotype was associated with a 2.42- and 9.46-fold increased risk of PTC (p < 0.0001). In addition, carriers of the TG or TT genotypes of rs4925166 and the AA genotype of rs372055 all presented a greater risk of PTC (prs4925166 = 0.0005, prs372055= 0.0021). Genetic model data further confirmed that the above four SNPs indeed increased the individual's sensitivity to PTC, as these SNPs were all associated with an elevated disease risk under different models (Bonferroni p < 0.0014). CONCLUSION: Our results revealed significant associations between amino acid metabolism gene polymorphisms and PTC risk, suggesting potential biomarkers for PTC susceptibility.