Abstract
The aim of the present study was to investigate whether genetic variants in the vascular endothelial growth factor A gene (VEGFA) were risk factors for papillary thyroid carcinoma (PTC) or nodular goiter (NG) in Han Chinese. A total of 2,319 subjects (861 PTC patients, 562 NG patients, and 896 healthy controls) were included. Five tag single nucleotide polymorphisms (tagSNPs: rs3024997, rs3025040, rs833070, rs25648, and rs10434) in VEGFA were genotyped. SNP rs3025040 T allele was associated with a decreased risk of NG (P<0.05). SNP rs3024997 was associated with an increased risk of PTC (P<0.05) and NG (P<0.001) when an over-dominant model (AA+GG vs. AG) was considered. PTC patients carry the less frequent TT genotype (compared to the CC genotype) (P <0.05) of SNP rs3025040. Likewise, NG patients have the less frequent TC genotype compared to the CC (P <0.05). No significant association of SNPs rs833070, rs25648, and rs10434 with PTC or NG was observed. Haplotypes AT (rs3024997 and rs3025040) and GTA (rs10434, rs3025040, and rs3024997) showed a lower risk for NG (P <0.01 and P <0.05, respectively), while haplotypes GTT (rs833070, rs3025040, and rs3024997) and GGGT (rs833070, rs10434, rs3024997, and rs3025040) predicted the risk of progression to NG (both P <0.05). Haplotype AGAC (rs833070, rs10434, rs3024997, and rs3025040) conferred protection for PTC (P <0.05). In summary, this study indicated for the first time that SNPs rs3024997 and rs3025040 in VEGFA were significantly associated with PTC and/or NG. Haplotypes of the VEGFA may influence the risk of PTC and NG.
Highlights
Thyroid cancer is one of the most common endocrine malignancies with a fairly rapid rising incidence throughout the world in recent years [1]
This study indicated for the first time that single nucleotide polymorphisms (SNPs) rs3024997 and rs3025040 in vascular endothelial growth factor A gene (VEGFA) were significantly associated with papillary thyroid carcinoma (PTC) and/ or nodular goiter (NG)
We investigated the association of tag SNPs in VEGFA and PTC and NG in a Han Chinese population
Summary
Thyroid cancer is one of the most common endocrine malignancies with a fairly rapid rising incidence throughout the world in recent years [1]. The risk factors for PTC include old age, extent of lymph node metastases, extra thyroidal invasion, distant metastasis, aggressive histological subtype, large tumor size, and terminal stage [6]. The prognosis of PTC appears to be relatively better than other types of cancer, cervical lymph node metastases and aggressive subset are the main contributors to poor prognosis [7]. NG is a common pathology of the thyroid gland, and varies in incidence in different parts of the world [8]. The incidence of thyroid cancer in multinodular goiter is estimated to be 5-10% [9]. The risk factors for NG include goiter size, www.impactjournals.com/oncotarget
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