Polymorphisms of IL-4 and IL-4R are associated to some demographic characteristics of differentiated thyroid cancer patients but are not determinants of risk in the Brazilian population.

BACKGROUND: IL-4 is known to present abnormal expression in thyroid tumors and SNPs in the IL-4 and its receptor IL-4R genes are associated to risk and mortality of various types of cancer. METHODS: In order to evaluate their role in differentiated thyroid cancer (DTC), we investigated genetic frequencies of two IL-4 promoter SNPs (rs2070874 C>T, rs2243250 C>T) and four non-synonymous SNPs of the IL-4R gene (rs1805010 A>G, rs1805012 C>T, rs1805013 C>T, rs1801275 A>G) in 300 DTC patients matched to 300 controls. All patients were managed according to current guidelines and followed-up for a period of 12-252 months (69.20 ± 52.70 months). RESULTS: Although none of the six investigated SNPs showed association with risk of DTC, rs1805010 was associated with age of diagnosis and the SNPs rs1805012 and rs1801275 were associated to gender. Further, in-silico analysis showed that all these three SNPs were able to cause decreased stability of the protein. We were not able to demonstrate any other association to clinical features of aggressiveness or to patients' prognosis. CONCLUSIONS: These findings indicate that although genetic variants in IL-4 and IL-4R do not influence the risk or outcome of DTC patients, their influence on the behavior of thyroid tumors deserves further investigation.

Interplay between Body Size Measures and Thyroid Cancer Aggressiveness: A Retrospective Analysis.

Considering controversial data about the relationship between body size and prognosis of differentiated thyroid cancer (DTC), the current study aimed to assess the influence of body weight, body mass index (BMI), and body surface area (BSA) on DTC. We conducted a retrospective analysis of patients' records from the Thyroid Cancer Unit, assessing body size measures, clinical and laboratory prognostic factors, and disease evolution. 337 patients, aged 45.95 ± 13.04 years old, with BMI of 27.87 ± 5.13 kg/m2 and BSA of 1.74 ± 0.18 m2 were enrolled. After 9.5 ± 6.9 years of follow-up, 87.29% of patients were disease-free and 12.71% had persistent disease; no patient had deceased. Patients aged <45 years old with extrathyroidal invasion tumor had greater baseline body weight and BSA than those without extrathyroidal invasion (median 79.5 kg versus 67 kg and 1.85 m2 versus 1.74 m2). Women with poorly differentiated tumor and patients aged ≥45 years old with distant metastasis presented greater weight loss during follow-up compared to patients without such characteristics (median -2 kg versus +1.5 kg and -3 kg versus +1 kg, respectively). The relationship between body size and DTC evolution was not observed. In conclusion, higher weight and BSA were associated with a greater chance of extrathyroidal tumor invasion in younger patients. Specific subgroups of patients with aggressive disease presented higher weight loss. Young patients with higher BSA should be carefully treated due to possible worse prognosis related to increased incidence of extrathyroid invasion. Findings related to tumor aggressiveness and weight loss in specific groups deserve further mechanistic studies.

Serum interleukin measurement may help identify thyroid cancer patients with active disease.

BACKGROUND: Investigate the clinical utility of serum interleukin dosages of IL-2, IL-2R, IL-4, IL-6, IL-6R, IL-8, IL-10 and IL-12 in the diagnosis and characterization of patients with DTC. In particular, verify ILs utility in the identification of individuals who are evolving disease-free or with the active disease. METHODS: We evaluated 200 patients with malignant nodules (100 patients disease-free and 100 patients with recurrence/active disease); 60 benign nodules and 100 healthy controls, serum levels were assessed by ELISA. RESULTS: All ILs, but not IL-4, differentiated these three groups. We observed that IL-2, 2R and 10 serum concentrations were associated with thyroglobulin levels. Serum IL-2 was able to differentiate patients with active disease from the disease-free with a sensitivity of 98%, specificity of 58%, positive predictive value (PPV) of 70% and negative predictive value (NPV) of 97% (p=0.0007). IL-6R levels differentiated patients with active disease from the disease-free patients with 56% sensitivity, 63% specificity, PPV of 60% and NPV of 59% (p<0.0001). IL-8 values also distinguished patients with active disease from the disease-free ones with sensitivity of 50%, specificity of 76%, PPV of 68% and NPV of 60% (p=0.0025); using IL-12, we obtained a sensitivity value of 73%, specificity of 66%, PPV of 68% and NPV of 71% (p<0.0001). Furthermore, interleukin levels showed association with some tumor characteristics of aggressiveness. CONCLUSION: We suggest that the serum concentration of ILs may assist in the diagnosis and characterization of tumor malignancy helping identify patients with active disease who deserve closer medical attention.