title: Associations of VEGF-C genetic polymorphisms with urothelial cell carcinoma susceptibility differ between smokers and non-smokers in Taiwan.
abstract: BACKGROUND
  Vascular 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.
  
  
  RESULTS
  Five 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of Surgery, Tungs' Taichung Metro Harbor Hospital, Taichung, Taiwan; Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Min-Che
authors.initials: MC
authors.lastname: Tung
authors.affiliation: Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Hsieh
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Shian-Shiang
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.affiliation: Division of Urology, Taipei City Hospital Renai Branch, Taipei, Taiwan; Department of Urology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Shiou-Sheng
authors.initials: SS
authors.lastname: Chen
authors.affiliation: Department of Medicine, Mackay Medical College, Taipei, Taiwan.
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Wang
authors.affiliation: Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Liang-Ming
authors.initials: LM
authors.lastname: Lee
authors.affiliation: Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wei-Jiunn
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan; Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Chien
mesh_terms: D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*; D013624:Taiwan; D014026:Nicotiana / Q000009:adverse effects; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics*
chemical_list: C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C