title: Impact of VEGF-C gene polymorphisms and environmental factors on oral cancer susceptibility in Taiwan.
abstract: BACKGROUND
  Oral cancer, which is the fourth most common male cancer, is associated with environmental carcinogens in Taiwan. Vascular endothelial growth factor (VEGF)-C, an angiogenic/lymphangiogenic factor with high expression levels in tumor tissues, plays important roles in the development of several malignancies. This study was designed to examine associations of five VEGF-C gene polymorphisms with the susceptibility to and clinicopathological characteristics of oral squamous cell carcinoma.
  
  
  RESULTS
  Five single-nucleotide polymorphisms (SNPs) of VEGF-C were analyzed by a real-time polymerase chain reaction (PCR) in 470 male patients with oral cancer and 426 cancer-free controls. In this study, we found that the VEGF-C rs7664413 and rs2046463 polymorphisms were associated with oral-cancer susceptibility but not with any clinicopathological parameters. The GGACA or GACTG haplotype of five VEGF-C SNPs (rs3775194, rs11947611, rs1485766, rs7664413, and rs2046463) combined was also related to the risk of oral cancer. Among 611 male smokers, VEGF-C polymorphism carriers who also chewed betel quid were found to have a 14.5-24.2-fold risk of having oral cancer compared to the VEGF-C wild-type carrier who did not chew betel quid. Among 461 male betel-quid chewers, VEGF-C polymorphism carriers who also smoked had a 2.7-18.1-fold risk of having oral cancer compared to those who carried the wild type but did not smoke.
  
  
  CONCLUSIONS
  Our results suggest that the two SNPs of VEGF-C (rs7664413 and rs2046463) and either of two haplotypes of five SNPs combined have potential predictive significance in oral carcinogenesis. Gene-environmental interactions among VEGF-C polymorphisms, smoking, and betel-quid chewing might alter one's susceptibility to oral cancer.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Chien
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Liu
authors.forename: Chung-Han
authors.initials: CH
authors.lastname: Hsin
authors.forename: Chien-Huang
authors.initials: CH
authors.lastname: Lin
authors.forename: Chun-Han
authors.initials: CH
authors.lastname: Shih
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.forename: Chao-Wen
authors.initials: CW
authors.lastname: Cheng
authors.forename: Chiao-Wen
authors.initials: CW
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D030561:Databases, Nucleic Acid; D004777:Environment; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000209:etiology*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013624:Taiwan; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics*
chemical_list: D042582:Vascular Endothelial Growth Factor C