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¹ Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC
² Graduate Institute of Medical Genetics, Kaohsiung Medical University, 100 TzYou First Road, Kaohsiung City 807, Taiwan, ROC
³ Health Center of Cimei Township, Public Health Bureau, Penghu County, Taiwan, ROC
⁴ Departments of Otorhinolaryngology and
⁵ Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC

(Correspondence should be addressed to S-H H Juo; Email: shj34{at}columbia.edu)

^* (P-J Hsiao and M-Y Lu contributed equally to this work)

Vascular endothelial growth factor (VEGF) is a potent stimulator for angiogenesis. It has been implicated in growth and metastasis of thyroid cancer. Three functional single nucleotide polymorphisms (SNPs) of VEGF (–2578C/A, –634G/C, and +936C/T) are known to be related with VEGF expression. We conducted a case–control study to evaluate the genetic effects of these three functional SNPs on the development of thyroid cancer and lymph node metastasis. A total of 332 cases and 261 controls were recruited for this study. The genotypes were determined by the TaqMan 5'-nuclease assay. Hardy–Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated by the ²-test and multiple logistic regression. We used Bonferroni correction to account for multiple testing, and a two-tailed P value <0.017 was considered statistically significant. All three SNPs were in HWE. The A allele of –2578C/A (i.e. SNP rs699947) increased a risk for thyroid cancer (adjusted OR=136, 95% CI=1.02–1.81, P=0.039). Haplotype analysis yielded a less significant result (an empirical P value of 0.07). There was a tendency of increasing the frequency of the risk allele from controls, patients without lymph node metastasis to patients with lymph node metastasis (P_trend=0.019). Further analysis showed that the genetic effect was only in men (adjusted OR=1.97, 95% CI=1.16–3.37, P=0.013) but not in women (adjusted OR=1.15, 95% CI=0.81–1.62, P=0.435). The other two SNPs did not show significant results. The A allele of the SNP rs699947 increased the risk of thyroid cancer development and regional lymph node metastasis in men.