TPO genetic variants and risk of differentiated thyroid carcinoma in two European populations.

Thyroid cancer risk involves the interaction of genetic and environmental factors. The thyroperoxidase (TPO) has a key role in the iodine metabolism, being essential for the thyroid function. Mutations in the TPO gene are common in congenital hypothyroidism, and there are also signs of the implication of TPO in thyroid cancer. We performed a case-control association study of genetic variants in TPO and differentiated thyroid carcinoma (DTC) in 1,586 DTC patients and 1,769 controls including two European populations (Italy: 1,190 DTC and 1,290 controls; Spain: 396 DTC and 479 controls). Multivariate logistic regression analyses were performed separately for each population and each single-nucleotide polymorphism (SNP). From the three studied polymorphisms, significant associations were detected between DTC and rs2048722 and rs732609 in both populations (p< 0.05). In the Italian population, both SNPs showed a negative association (rs2048722, odds ratio [OR]=0.79, 95% confidence interval [CI]=0.63-1.00, p=0.045; rs732609, OR=0.72, 95% CI=0.55-0.94, p=0.016), whereas in the Spanish population, these SNPs showed a positive association (rs2048722, OR=1.39, 95% CI=1.03-1.89, p=0.033; rs732609, OR=1.41, 95% CI=1.06-1.87, p=0.018). The corresponding associations for papillary or follicular thyroid cancer were similar to those for all DTC, within population. No association was detected for the third TPO polymorphism in the Italian and the Spanish populations. Our results, for the first time, point to TPO as a gene involved in the risk of DTC, and suggest the importance of interactions between TPO variants and other unidentified population-specific factors in determining thyroid cancer risk.