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

Abstract

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] 5 0.79, 95% confidence interval [CI] 5 0.63-1.00, p 5 0.045; rs732609, OR 5 0.72, 95% CI 5 0.55-0.94, p 5 0.016), whereas in the Spanish population, these SNPs showed a positive association (rs2048722, OR 5 1.39, 95% CI 5 1.03-1.89, p 5 0.033; rs732609, OR 5 1.41, 95% CI 5 1.06-1.87, p 5 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.Differentiated thyroid carcinoma (DTC) comprises papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) histological subtypes and it accounts for 90% of thyroid neoplasms.1 In the last two decades, the incidence of thyroid cancer (TC) in developed countries has been increasing, particularly for PTC.2,3 It has been proposed that the main component in TC predisposition resides in the interaction of genetic variants (e.g., single-nucleotide polymorphisms [SNPs]) with environmental factors.1,4-6 Environment could explain, at least in part, local regional variations in the

Identification of CHEK1, SLC26A4, c-KIT, TPO and TG as new biomarkers for human follicular thyroid carcinoma

“…With regard to the strong downregulation of c-KIT observed by us in FTC (Table 1), to the best of our knowledge such downregulation has not been previously associated with human FTC, while a similar tendency has been previously reported in PTC by us and others [8]. Finally, in an agreement with the previously established role of thyroid peroxidase ( TPO ) in oncogenic transformation in general, and its association with human thyroid carcinomas [23, 24], our analysis has shown a strong downregulation of this transcript in all FTC samples (Table 1). …”

Asbestos‐associated genome‐wide DNA methylation changes in lung cancer

“…TPO encodes thyroid peroxidase involved in oxidative metabolic reactions, mostly studied in thyroid cells. 31 Of note in this context is that asbestos-related mechanisms of carcinogenesis are known to involve reactive oxygen species (ROS). 32 To follow this line of speculative points, it is interesting that increased expression of TPO has been observed in tumor/lung tissue of adenocarcinoma patients with high intakes of red meat; the increased expression was attributed to a gene product linked to heme-iron toxicity and oxidative stress.…”

Large thyroid cyst in a patient with congenital hypothyroidism

“…Again, not only elevated TSH levels (15,16) but also primary genetic abnormality including TPO (17)(18)(19) and thyroglobulin gene mutations may further prone these patients to thyroid cancer particularly in those with thyroglobulin gene mutations (20,21). In this regard, polymorphisms in the exon 10-12 cluster (22), biallelic p.R2223H mutation (19), activating mutation of V599E or K600E (20), g.IVS5 + 1G-->A (23) and R-allele of Tg Q2511R (24) have been associated with higher risk of malignant transformation. Even non goitrous glands in patients with thyroid hormone biosynthetic defects may undergo malignant transformation (25).…”