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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, METHODS, METHODS, METHODS, RESULTS. Meshes: Adult, Aged, Biomarkers, Tumor, Disease-Free Survival, Female, Follow-Up Studies, Genotype, Humans, Male, Microvessels, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Neovascularization, Pathologic, Polymorphism, Single Nucleotide, Prognosis, Retrospective Studies, Thyroid Neoplasms, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-2, Young Adult.
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Do germline polymorphisms of the VEGF-pathway predict recurrence in non-advanced differentiated thyroid cancer? Context: Angiogenesis is an hallmark of cancer and is mainly determined by genetic background, rather than environment. Germline single nucleotide polymorphisms (SNPs) of VEGF-pathway have demonstrated prognostic value in different tumours. Main: testing prognostic value of germline SNPs of VEGF-pathway in non-advanced DTC. Secondary: correlating analyzed SNPs with microvessel density (MVD). Multicenter, retrospective, observational study. Four referral centers. Blood samples were obtained from consecutive DTC patients. SNP genotyping was performed according to TaqMan protocol, including 4 VEGF-A (-2578C>A, -460T>C, +405G>C, and +936C>T) and 2 VEGFR-2 (+1192 C>T and +1719 T>A) SNPs. MVD was estimated by means of CD34 staining. Main outcome meausures: Rate of recurrent structural disease/disease free survival (DFS). Difference in MVD between tumours from patients with different genotype. Two-hundred four AJCC/UICC stage I-II (mean follow-up 73±64 months) and 240 ATA low-intermediate risk DTC (mean follow-up 70±60 months) were enrolled. We identified 2 "risk" genotypes by combining VEGF-A SNPs -2578 C>A, -460 T>C, and +405 G>C. ACG homozygous genotype was protective in both stage I-II (p=0.018, OR=0.08, 95% CI 0.01-1.43) and ATA low-intermediate risk (p=0.035, OR=0.14, 95% CI 0.01-1.13) patients. CTG homozygous genotype was significantly associated to recurrence in stage I-II (p=0.018, OR=5.47, 95% CI 1.15-26.04), and was slightly deleterious in ATA low-intermediate risk (p=0.079, OR=3.39, 95% 0.8-14.33) subjects. MVD of primary tumours from patients harbouring protective genotype was significantly lower (median MVD 76.5±12.7 and 86.7±27.9, respectively; p=0.024).
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Analysis of germline VEGF-A SNPs could empower prognostic approach to DTC. Further validation is required. Final Decision: yes