TY - JOUR
T1 - Germline polymorphisms of the VEGF pathway predict recurrence in nonadvanced differentiated thyroid cancer
AU - Marotta, Vincenzo
AU - Sciammarella, Concetta
AU - Capasso, Mario
AU - Testori, Alessandro
AU - Pivonello, Claudia
AU - Chiofalo, Maria Grazia
AU - Ambardella, Claudio
AU - Grasso, Marica
AU - Antonino, Antonio
AU - Annunziata, Annamaria
AU - Macchia, Paolo Emidio
AU - Pivonello, Rosario
AU - Santini, Luigi
AU - Botti, Gerardo
AU - Losito, Simona
AU - Pezzullo, Luciano
AU - Colao, Annamaria
AU - Faggiano, Antongiulio
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Context: Tumor angiogenesis is determined by host genetic background rather than environment. Germline single nucleotide polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) pathway have demonstrated prognostic value in different tumors. Objectives: Our main objective was to test the prognostic value of germline SNPs of the VEGF pathway in nonadvanced differentiated thyroid cancer (DTC). Secondarily, we sought to correlate analyzed SNPs with microvessel density (MVD). Design: Multicenter, retrospective, observational study. Setting: Four referral centers. Patients: Blood samples were obtained from consecutive DTC patients. Genotyping was performed according to the TaqMan protocol, including 4 VEGF-A (22578C>A, 2460T>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. Outcome Measures: Rate of recurrent structural disease/disease-free survival (DFS). Difference in MVD between tumors from patients with different genotype. Results: Two hundred four patients with stage I-II DTC (mean follow-up, 73 ± 64 months) and 240 patients with low-to intermediate-risk DTC (mean follow-up, 70 6 60 months) were enrolled. Two "risk" genotypes were identified by combining VEGF-A SNPs 22578 C>A, 2460 T>C, and +405 G>C. The ACG homozygous genotype was protective in both stage I-II (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.01 to 1.43; P = 0.018) and low-to intermediate-risk (OR, 0.14; 95% CI, 0.01 to 1.13; P = 0.035) patients. The CTG homozygous genotype was significantly associated with recurrence in stage I-II (OR, 5.47; 95% CI, 1.15 to 26.04; P = 0.018) andwas slightly deleterious in lowto intermediate-risk (OR, 3.39; 95%CI, 0.8 to 14.33; P = 0.079) patients.MVD of primary tumors from patients harboring a protective genotype was significantly lower (median MVD, 76.5 ± 12.7 and 86.7 ± 27.9, respectively; P = 0.024). Conclusions: Analysis of germline VEGF-A SNPs could empower a prognostic approach to DTC.
AB - Context: Tumor angiogenesis is determined by host genetic background rather than environment. Germline single nucleotide polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) pathway have demonstrated prognostic value in different tumors. Objectives: Our main objective was to test the prognostic value of germline SNPs of the VEGF pathway in nonadvanced differentiated thyroid cancer (DTC). Secondarily, we sought to correlate analyzed SNPs with microvessel density (MVD). Design: Multicenter, retrospective, observational study. Setting: Four referral centers. Patients: Blood samples were obtained from consecutive DTC patients. Genotyping was performed according to the TaqMan protocol, including 4 VEGF-A (22578C>A, 2460T>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. Outcome Measures: Rate of recurrent structural disease/disease-free survival (DFS). Difference in MVD between tumors from patients with different genotype. Results: Two hundred four patients with stage I-II DTC (mean follow-up, 73 ± 64 months) and 240 patients with low-to intermediate-risk DTC (mean follow-up, 70 6 60 months) were enrolled. Two "risk" genotypes were identified by combining VEGF-A SNPs 22578 C>A, 2460 T>C, and +405 G>C. The ACG homozygous genotype was protective in both stage I-II (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.01 to 1.43; P = 0.018) and low-to intermediate-risk (OR, 0.14; 95% CI, 0.01 to 1.13; P = 0.035) patients. The CTG homozygous genotype was significantly associated with recurrence in stage I-II (OR, 5.47; 95% CI, 1.15 to 26.04; P = 0.018) andwas slightly deleterious in lowto intermediate-risk (OR, 3.39; 95%CI, 0.8 to 14.33; P = 0.079) patients.MVD of primary tumors from patients harboring a protective genotype was significantly lower (median MVD, 76.5 ± 12.7 and 86.7 ± 27.9, respectively; P = 0.024). Conclusions: Analysis of germline VEGF-A SNPs could empower a prognostic approach to DTC.
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U2 - 10.1210/jc.2016-2555
DO - 10.1210/jc.2016-2555
M3 - Article
AN - SCOPUS:85012054073
VL - 102
SP - 661
EP - 671
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 2
ER -