Abstract
BackgroundVascular endothelial growth factor (VEGF)-C is associated with lymphangiogenesis, pelvic regional lymph node metastasis, and an antiapoptotic phenotype in urothelial cell carcinoma (UCC). Knowledge of potential roles of VEGF-C genetic polymorphisms in susceptibility to UCC is lacking. This study was designed to examine associations between VEGF-C gene variants and UCC susceptibility and evaluate whether they are modified by smoking.Methodology/Principal FindingsFive single-nucleotide polymorphisms (SNPs) of VEGF-C were analyzed by a TaqMan-based real-time polymerase chain reaction (PCR) in 233 patients with UCC and 520 cancer-free controls. A multivariate logistic regression was applied to model associations between genetic polymorphisms and UCC susceptibility, and to determine if the effect was modified by smoking. We found that after adjusting for other covariates, individuals within the entire population and the 476 non-smokers carrying at least one A allele at VEGF-C rs1485766 respectively had 1.742- and 1.834-fold risks of developing UCC than did wild-type (CC) carriers. Among the 277 smokers, we found that VEGF-C rs7664413 T (CT+TT) and rs2046463 G (AG+GG) allelic carriers were more prevalent in UCC patients than in non-cancer participants. Moreover, UCC patients with the smoking habit who had at least one T allele of VEGF-C rs7664413 were at higher risk of developing larger tumor sizes (p = 0.021), compared to those patients with CC homozygotes.ConclusionsOur results suggest that the involvement of VEGF-C genotypes in UCC risk differs among smokers compared to non-smokers among Taiwanese. The genetic polymorphism of VEGF-C rs7664413 might be a predictive factor for the tumor size of UCC patients who have a smoking habit.
Highlights
Urothelial cell carcinoma (UCC) is the second most common cancer and second leading cause of death among malignancies of the genitourinary tract system in the US [1]
Our results suggest that the involvement of Vascular endothelial growth factor (VEGF)-C genotypes in urothelial cell carcinoma (UCC) risk differs among smokers compared to non-smokers among Taiwanese
The genetic polymorphism of VEGF-C rs7664413 might be a predictive factor for the tumor size of UCC patients who have a smoking habit
Summary
Urothelial cell carcinoma (UCC) is the second most common cancer and second leading cause of death among malignancies of the genitourinary tract system in the US [1]. Many previous studies demonstrated that tumor-associated angiogenesis and lymphangiogenesis play crucial roles in tumor progression, and angiogenic and lymphangiogenic activities are frequently correlated with tumor growth, regional lymph-node metastasis, distant metastasis, and the prognosis of patients with malignant neoplasms [7,8]. Overexpression of VEGF-C in bladder UCC was shown to be significantly related to tumor size, pathological T stage, lymphatic-venous involvement, and pelvic lymph node metastasis [10]. Upregulation of VEGF-C was shown to play an important role in cigarette smoking-associated cervical tumorigenesis [12], but the association between VEGF-C and cigarette smoking in UCC is still unknown. Vascular endothelial growth factor (VEGF)-C is associated with lymphangiogenesis, pelvic regional lymph node metastasis, and an antiapoptotic phenotype in urothelial cell carcinoma (UCC). This study was designed to examine associations between VEGF-C gene variants and UCC susceptibility and evaluate whether they are modified by smoking
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